Recent developments on 1,2,4-triazole nucleus in anticancer compounds: A review

Anti-Cancer Agents in Medicinal Chemistry

Volumn 16, Issue 4, 2016, Pages 465-489

  Kaur, Ramandeep ^a   Dwivedi, Ashish Ranjan ^a   Kumar, Bhupinder ^a   Kumar, Vinod ^a  

^a CENTRAL UNIVERSITY OF PUNJAB   (India)

Author keywords

1,2,4 triazoles; Anticancer; Kinase inhibitors; Structure activity relationship; Tubulin modulators

Indexed keywords

1,2,4 TRIAZOLE DERIVATIVE; ABELSON KINASE; ACTIVIN RECEPTOR LIKE KINASE 1; ANTINEOPLASTIC AGENT; AROMATASE; BENZOTHIAZOLE DERIVATIVE; CASPASE 3; CISPLATIN; CLADRIBINE; EPIDERMAL GROWTH FACTOR RECEPTOR; GEMCITABINE; HEAT SHOCK PROTEIN 27; IMATINIB; LETROZOLE; METHIONYL AMINOPEPTIDASE; NUCLEOSIDE DERIVATIVE; PACLITAXEL; PROTEIN KINASE INHIBITOR; PROTEIN P53; PROTEIN TYROSINE PHOSPHATASE; REACTIVE OXYGEN METABOLITE; RIBAVIRIN; RIBAVIRIN DERIVATIVE; STRESS ACTIVATED PROTEIN KINASE; SULFATASE; TANKYRASE INHIBITOR; TOLL LIKE RECEPTOR 7; TUBULIN MODULATOR; UNINDEXED DRUG; VOROZOLE; 1,2,4-TRIAZOLE; TRIAZOLE DERIVATIVE;

ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; CELL CYCLE ARREST; CELLULAR IMMUNITY; CLINICAL TRIAL (TOPIC); CYTOTOXICITY; DRUG RECEPTOR BINDING; HEPATITIS C VIRUS; HUMAN; HYDROGEN BOND; IC50; LUCIFERASE ASSAY; MTT ASSAY; PHARMACOPHORE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; RECEPTOR DOWN REGULATION; REVIEW; STRUCTURE ACTIVITY RELATION; ANIMAL; CELL PROLIFERATION; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; DRUG SCREENING;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL PROLIFERATION; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; MOLECULAR STRUCTURE; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZOLES;

EID: 84961583757     PISSN: 18715206     EISSN: 18755992     Source Type: Journal    
DOI: 10.2174/1871520615666150819121106     Document Type: Review

References (191)

1. Carter, K.; Miller, R.; Hedrick, J. Synthesis and properties of imide-aryl ether 1, 2, 4-triazole random copolymers. Polymer., 1993, 34, 843-848.
2. Vatmurge, N.S.; Hazra, B.G.; Pore, V.S.; Shirazi, F.; Chavan, P.S.; Deshpande, M.V. Synthesis and antimicrobial activity of ß-lactam– bile acid conjugates linked via triazole. Bioorg. Med. Chem. Lett., 2008, 18, 2043-2047.
3. Chohan, Z.H.; Sumrra, S.H.; Youssoufi, M.H.; Hadda, T.B. Metal based biologically active compounds: Design, synthesis, and antibacterial/antifungal/cytotoxic properties of triazole-derived Schiff bases and their oxovanadium (IV) complexes. Eur. J. Med. Chem., 2010, 45, 2739-2747.
4. Navidpour, L.; Shafaroodi, H.; Abdi, K.; Amini, M.; Ghahremani, M.H.; Dehpour, A.R.; Shafiee, A., Design, synthesis, and biological evaluation of substituted 3-alkylthio-4,5-diaryl-4H-1,2,4-triazoles as selective COX-2 inhibitors. Bioorg. Med. Chem., 2006, 14, 2507-2517.
5. Okuno, T.O.; S Goto, T.; Sawai, K.; Shirahama, H.; Matsumoto, T., structures and phytotoxicity of metabolites from Valsa ceratosperma. Agic. Biol. Chem., 1986, 50, 997-1001.
6. Blank, B.; Nichols, D.M.; Vaidya, P.D. Synthesis of 1, 2, 4- triazoles as potential Hypoglycemic Agents. J. Med. Chem., 1972, 15, 694-696.
7. Bokor, E.; Docsa, T.; Gergely, P.; Somsak, L. C-Glucopyranosyl-1, 2, 4-triazoles as new potent inhibitors of glycogen phosphorylase. ACS Med. Chem. Lett., 2013, 4, 612-615.
8. Radhika, C.; Venkatesham, A.; Sarangapani, M., Synthesis and antidepressant activity of di substituted-5-aryl-1, 2, 4-triazoles. Med. Chem. Res., 2012, 21, 3509-3513.
9. Ainsworth, C.; Easton, N.R.; Livezey, M.; Morrison, D.; Gibson, W. The anticonvulsant activity of 1, 2, 4-triazoles. J. Med. Chem., 1962, 5, 383-389.
10. Boechat, N.; Pinheiro, L.; Santos-Filho, O.A.; Silva, I.C. Design and Synthesis of New N-(5-Trifluoromethyl)-1H-1, 2, 4-triazol-3- yl benzenesulfonamides as possible antimalarial prototypes. Molecules, 2011, 16, 8083-8097.
11. Nubia Boechat, L.C.S.P.; Osvaldo, A.; Santos-Filho, O.A.; Isabor, C. Silva Design and Synthesis of New N-(5-Trifluoromethyl)-1H- 1,2,4-triazol-3-yl benzenesulfonamides as possible antimalarial prototypes. APB, 2013, 3, 13-18.
12. Williamson, D.J.; Hill, R.G.; Shepheard, S.L.; Hargreaves, R.J. The anti_migraine 5_HT1B/1D agonist rizatriptan inhibits neurogenic dural vasodilation in anaesthetized guinea_pigs. Br. J. Pharmacol., 2001, 133, 1029-1034.
13. Malerich, J.P.; Lam, J.S.; Hart, B.; Fine, R.M.; Klebansky, B.; Tanga, M.J.; D’Andrea, A. Diamino-1, 2, 4-triazole derivatives are selective inhibitors of TYK2 and JAK1 over JAK2 and JAK3. Bioorg. Med. Chem. Lett., 2010, 20, 7454-7457.
14. Maletic, M.; Leeman, A.; Szymonifka, M.; Mundt, S.S.; Zokian, H.J.; Shah, K.; Dragovic, J.; Lyons, K.; Thieringer, R.; Vosatka, A.H. Bicyclo [2.2. 2] octyltriazole inhibitors of 11ß-hydoxysteroid dehydrogenase type 1. Pharmacological agents for the treatment of metabolic syndrome. Bioorg. Med. Chem. Lett., 2011, 21, 2568-2572.
15. Di Mola, N.; Bellasio, E., Potential antihypertensives. Synthesis of 6-substituted-N-(4H-1, 2, 4-triazol-4-yl)-3-pyridazinamines and 3- substituted-6-(3, 5-dimethyl-1H-1, 2, 4-triazol-1-yl) pyridazines. Farmaco-Ed. Sci., 1985, 40, 517-533.
16. Jordao, A.K.; Afonso, P.P.; Ferreira, V.F.; De Souza, M.C.; Almeida, M.C.; Beltrame, C.O.; Paiva, D.P.; Wardell, S.M.; Wardell, J.L.; Tiekink, E.R. Antiviral evaluation of N-amino-1,2,3- triazoles against Cantagalo virus replication in cell culture. Eur. J. Med. Chem., 2009, 44, 3777-3783.
17. Valda Rodriguez, L.; Dedet, J.P.; Paredtes, V.; Mendoza, C.; Cardenas, F. A randomized trial of amphotericin B alone or in combination with itraconazole in the treatment of mucocutaneous leishmaniasis. Mem. I Oswaldo. Cruz., 1995, 90, 525-528.
18. Calderone, V.; Giorgi, I.; Livi, O.; Martinotti, E.; Mantuano, E.; Martelli, A.; Nardi, A. Benzoyl and/or benzyl substituted 1, 2, 3- triazoles as potassium channel activators. VIII. Eur. J. Med. Chem., 2005, 40, 521-528.
19. Jordao, A.K.; Ferreira, V.F.; Lima, E.S.; De Souza, M.C.; Carlos, E.C.; Castro, H.C.; Geraldo, R.B.; Rodrigues, C.R.; Almeida, M.C.; Cunha, A.C., Synthesis, antiplatelet and in silico evaluations of novel N-substituted-phenylamino-5-methyl-H-1, 2, 3-triazole-4- carbohydrazides. Bioorg. Med. Chem., 2009, 17, 3713-3719.
20. Ilango, K.; Valentina, P., Synthesis and biological activities of novel 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazoles. Der. Pharma. Chem., 2010, 2, 16-22.
21. He, J.; Feng, L.; Li, J.; Tao, R.; Wang, F.; Liao, X.; Sun, Q.; Long, Q.; Ren, Y.; Wan, J. Design, synthesis and biological evaluation of novel 2-methylpyrimidine-4-ylamine derivatives as inhibitors of Escherichia coli pyruvate dehydrogenase complex E1. Bioorg. Med. Chem., 2012, 20, 1665-1670.
22. Oh, K.; Yamada, K.; Asami, T.; Yoshizawa, Y. Synthesis of novel brassinosteroid biosynthesis inhibitors based on the ketoconazole scaffold. Bioorg. Med. Chem. Lett., 2012, 22, 1625-1628.
23. Wang, S.; Li, Q.S.; Su, M.G., Solubility of 1 H-1, 2, 4-Triazole in Ethanol, 1-Propanol, 2-Propanol, 1, 2-Propanediol, Ethyl formate, Methyl Acetate, Ethyl acetate and Butyl acetate at (283 to 363) K. J. Chem. Eng. Data, 2007, 52, 856-858.
24. Moulin, A.; Bibian, M.; Blayo, A.L.; El Habnouni, S.; Martinez, J.; Fehrentz, J.A., Synthesis of 3, 4, 5-Trisubstituted-1, 2, 4- triazoles. Chem. Rev., 2010, 110, 1809-1827
25. Holm, S.C.; Straub, B.F., Synthesis of N-Substituted 1, 2, 4-Triazoles. A review. Org. Prep. Proced. Int., 2011, 43, 319-347.
26. Sahoo, S.; Veliyath, S., Review on substituted 1, 2, 4-triazoles as potent antifungal and antibacterial agents. Int. J. Res. Pharm. Sci., 2012, 3, 326-333
27. Küçükgüzel, S.G.; Çikla-Süzgün, P. Recent advances bioactive 1, 2, 4-triazole-3-thiones. Eur. J. Med. Chem., 2014.
28. Herdewijn, P., Modified nucleosides: in biochemistry, biotechnology and medicine. 2008: John Wiley & Sons-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany.
29. De Clercq, E. The design of drugs for HIV and HCV. Nat. Rev. Drug Discov., 2007, 6, 1001-1018.
30. Ogawa, K.; Hige, S.; Nakanishi, M.; Yamamoto, Y.; Chuma, M.; Nagasaka, A.; Asaka, M. Immunological and mutagenic actions of ribavirin monotherapy preceding combination therapy with interferon for patients with chronic hepatitis C. Antivi. Ther., 2009, 14, 513-522.
31. Beutler, E., Cladribine (2-chlorodeoxyadenosine). The Lancet 1992, 340, 952-956
32. Christensen, L.F.; Broom, A.D.; Robins, M.J.; Bloch, A., Synthesis and biological activity of selected 2, 6- disubstituted (2-deoxy-. alpha.-and-. beta.-D-erythropentofuranosyl) purines. J. Med. Chem., 1972, 15, 735-739.
33. Kini, G.D.; Robins, R.K.; Avery, T.L., Synthesis and antitumor activity of ribavirin imidates. New facile synthesis of ribavirin amidine (1-. beta.-D-ribofuranosyl-1, 2, 4-triazole-3-carboxamidine hydrochloride). J. Med. Chem., 1989, 32, 1447-1449.
34. Ding, Y.; Zhang, Y.Y.; Zhang, J.; Chen, Y.Q., Syntheses and anticancer activity of ribonucleoside analogues containing thiosubstituted five-membered heterocyclic base. Bioorg. Med. Chem. Lett., 1997, 7, 1607-1610.
35. Wan, J.; Xia, Y.; Liu, Y.; Wang, M.; Rocchi, P.; Yao, J.; Qu, F.; Neyts, J.; Iovanna, J.L.; Peng, L. Discovery of novel arylethynyltriazole ribonucleosides with selective and effective antiviral and anti-proliferative activity. J. Med. Chem., 2009, 52, 1144-1155.
36. Xia, Y.; Liu, Y.; Wan, J.; Wang, M.; Rocchi, P.; Qu, F.; Iovanna, J.L.; Peng, L., Novel triazole ribonucleoside down-regulates heat shock protein 27 and induces potent anticancer activity on drug-resistant pancreatic cancer. J. Med. Chem., 2009, 52, 6083-6096.
37. Xia, Y.; Liu, Y.; Rocchi, P.; Wang, M.; Fan, Y.; Qu, F.; Iovanna, J.L.; Peng, L. Targeting heat shock factor 1 with a triazole nucleoside analog to elicit potent anticancer activity on drugresistant pancreatic cancer. Cancer Lett., 2012, 318, 145-153.
38. Liu, Y.; Xia, Y.; Fan, Y.; Maggiani, A.; Rocchi, P.; Qu, F.; Iovanna, J.L.; Peng, L. N-Aryltriazole ribonucleosides with potent anti-proliferative activity against drug-resistant pancreatic cancer. Bioorg. Med. Chem. Lett., 2010, 20, 2503-2507.
39. Wang, M.; Xia, Y.; Fan, Y.; Rocchi, P.; Qu, F.; Iovanna, J.L.; Peng, L. A novel arylethynyltriazole acyclonucleoside inhibits proliferation of drug-resistant pancreatic cancer cells. Bioorg. Med. Chem. Lett., 2010, 20, 5979-5983.
40. Xia, Y.; Wang, M.; Demaria, O.; Tang, J.; Rocchi, P.; Qu, F.; Iovanna, J.L.; Alexopoulou, L.; Peng, L., A novel bitriazolyl acyclonucleoside endowed with dual anti-proliferative and immunomodulatory activity. J. Med. Chem., 2012, 55, 5642-5646.
41. Avanzo, R.E.; Anesini, C.; Fascio, M.L.; Errea, M.I.; D’Accorso, N.B., 1, 2, 4-Triazole d-ribose derivatives: design, synthesis and antitumoral evaluation. Eur. J. Med. Chem., 2012, 47, 104-110.
42. Zhang, J.; Yang, P.L.; Gray, N.S. Targeting cancer with small molecule kinase inhibitors. Nat. Rev. Cancer, 2009, 9, 28-39.
43. Bharate, S.B.; Sawant, S.D.; Singh, P.P.; Vishwakarma, R.A., Kinase inhibitors of marine origin. Chem. Rev., 2013, 113, 6761-6815.
44. Dae-Kee Kim, J.K.A.H.J.P. Design, synthesis and biological evaluation of novel 2-pyridinyl-[1,2,4]triazoles as inhibitors of transforming growth factor b1 type 1 receptor. Bioorg. Med. Chem., 2004, 12, 2013-2020.
45. Lin, R.; Connolly, P.J.; Huang, S.; Wetter, S.K.; Lu, Y.; Murray, W.V.; Emanuel, S.L.; Gruninger, R.H.; Fuentes-Pesquera, A.R.; Rugg, C.A., 1-Acyl-1 H-[1, 2, 4] triazole-3, 5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities. J. Med. Chem., 2005, 48, 4208-4211.
46. Salah, E.; Ugochukwu, E.; Barr, A.J.; Von Delft, F.; Knapp, S.; Elkins, J.M., Crystal structures of ABL-related gene (ABL2) in complex with imatinib, tozasertib (VX-680) and a type I inhibitor of the triazole carbothioamide class. J. Med. Chem., 2011, 54, 2359-2367.
47. De, S.K.; Stebbins, J.L.; Chen, L.H.; Riel-Mehan, M.; Machleidt, T.; Dahl, R.; Yuan, H.; Emdadi, A.; Barile, E.; Chen, V. Design, synthesis, and structure- activity relationship of substrate competitive, selective, and in vivo active triazole and thiadiazole inhibitors of the c-jun n-terminal kinase. J. Med. Chem., 2009, 52, 1943-1952.
48. Park, H.; Bahn, Y.J.; Jeong, D.G.; Woo, E.J.; Kwon, J.S.; Ryu, S.E. Identification of novel inhibitors of extracellular signal-regulated kinase 2 based on the structure-based virtual screening. Bioorg. Med. Chem. Lett., 2008, 18, 5372-5376.
49. Wu, Z.; Hartnett, J.C.; Neilson, L.A.; Robinson, R.G.; Fu, S.; Barnett, S.F.; Defeo-Jones, D.; Jones, R.E.; Kral, A.M.; Huber, H.E. Development of pyridopyrimidines as potent Akt1/2 inhibitors. Bioorg. Med. Chem. Lett., 2008, 18, 1274-1279.
50. Siu, T.; Liang, J.; Arruda, J.; Li, Y.; Jones, R.E.; Defeo-Jones, D.; Barnett, S.F.; Robinson, R.G. Discovery of potent and cell-active allosteric dual Akt 1 and 2 inhibitors. Bioorg. Med. Chem. Lett., 2008, 18, 4186-4190.
51. George, R.E.; Sanda, T.; Hanna, M.; Fröhling, S.; Luther, W.; Zhang, J.; Ahn, Y.; Zhou, W.; London, W.B.; McGrady, P., Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature, 2008, 455, 975-978.
52. Deng, X.; Wang, J.; Zhang, J.; Sim, T.; Kim, N.D.; Sasaki, T.; Luther, W.; George, R.E.; Jänne, P.A.; Gray, N.S. Discovery of 3, 5-diamino-1, 2, 4-triazole ureas as potent anaplastic lymphoma kinase inhibitors. ACS Med. Chem. Lett., 2011, 2, 379-384.
53. Park, H.; Bahn, Y.J.; Jung, S.K.; Jeong, D.G.; Lee, S.H.; Seo, I.; Yoon, T.S.; Kim, S.J.; Ryu, S.E. Discovery of novel Cdc25 phosphatase inhibitors with micromolar activity based on the structure-based virtual screening. J. Med. Chem., 2008, 51, 5533-5541.
54. Park, H.; Bahn, Y.J.; Ryu, S.E., Structure-based de novo design and biochemical evaluation of novel Cdc25 phosphatase inhibitors. Bioorg. Med. Chem. Lett., 2009, 19, 4330-4334.
55. Zhang, Y.B.; Liu, W.; Yang, Y.S.; Wang, X.L.; Zhu, H.L.; Bai, L.F.; Qiu, X.Y. Synthesis, molecular modeling, and biological evaluation of 1, 2, 4-triazole derivatives containing pyridine as potential anti-tumor agents. Med. Chem. Res., 2013, 22, 1-11.
56. Xu, F.; Jia, Y.; Wen, Q.; Wang, X.; Zhang, L.; Zhang, Y.; Yang, K.; Xu, W. Synthesis and biological evaluation of N-(4-hydroxy-3- mercaptonaphthalen-1-yl) amides as inhibitors of angiogenesis and tumor growth. Eur. J. Med. Chem. 2013, 64, 377-388.
57. Dinges, J.; Albert, D.H.; Arnold, L.D.; Ashworth, K.L.; Akritopoulou-Zanze, I.; Bousquet, P.F.; Bouska, J.J.; Cunha, G.A.; Davidsen, S.K.; Diaz, G.J. 1, 4-Dihydroindeno [1, 2-c] pyrazoles with acetylenic side chains as novel and potent multitargeted receptor tyrosine kinase inhibitors with low affinity for the hERG ion channel. J. Med. Chem., 2007, 50, 2011-2029.
58. Yates, P.C.; Mccall, C.J.; Stevens, M.F. Structural studies on benzothiazoles. Crystal and molecular structure of 5, 6-dimethoxy- 2-4-methoxyphenyl-benzothiazole and molecular orbital calculations on related compounds. Tetrahedron, 1991, 47, 6493-6502.
59. Ibrahim, D., Synthesis and biological evaluation of 3, 6-disubstituted [1, 2, 4] triazolo [3, 4-b][1, 3, 4] thiadiazole derivatives as a novel class of potential anti-tumor agents. Eur. J. Med. Chem., 2009, 44, 2776-2781.
60. Abou-Seri, S.M. Synthesis and biological evaluation of novel 2, 4'- bis substituted diphenylamines as anticancer agents and potential epidermal growth factor receptor tyrosine kinase inhibitors. Eur. J. Med. Chem., 2010, 45, 4113-4121.
61. Ouyang, X.; Chen, X.; Piatnitski, E.L.; Kiselyov, A.S.; He, H.Y.; Mao, Y.; Pattaropong, V.; Yu, Y.; Kim, K.H.; Kincaid, J., Synthesis and structure–activity relationships of 1, 2, 4-triazoles as a novel class of potent tubulin polymerization inhibitors. Bioorg. Med. Chem. Lett., 2005, 15, 5154-5159.
62. Pettit, G.R.; Rhodes, M.R.; Herald, D.L.; Hamel, E.; Schmidt, J.M.; Pettit, R.K. Antineoplastic Agents. 445. Synthesis and evaluation of structural modifications of (Z)-and (E)-Combretastatin A-4 1. J. Med. Chem., 2005, 48, 4087-4099.
63. Zhang, Q.; Peng, Y.; Wang, X.I.; Keenan, S.M.; Arora, S.; Welsh, W.J. Highly potent triazole-based tubulin polymerization inhibitors. J. Med. Chem., 2007, 50, 749-754.
64. Romagnoli, R.; Baraldi, P.G.; Cruz-Lopez, O.; Lopez Cara, C.; Carrion, M.D.; Brancale, A.; Hamel, E.; Chen, L.; Bortolozzi, R.; Basso, G., Synthesis and antitumor activity of 1, 5-disubstituted 1, 2, 4-triazoles as cis-restricted combretastatin analogues. J. Med. Chem., 2010, 53, 4248-4258.
65. Zhang, N.; Ayral-Kaloustian, S.; Nguyen, T.; Afragola, J.; Hernandez, R.; Lucas, J.; Gibbons, J.; Beyer, C., Synthesis and SAR of [1, 2, 4] triazolo [1, 5-a] pyrimidines, a class of anticancer agents with a unique mechanism of tubulin inhibition. J. Med. Chem., 2007, 50, 319-327.
66. Lee, J.; Kim, S.J.; Choi, H.; Kim, Y.H.; Lim, I.T.; Yang, H.M.; Lee, C.S.; Kang, H.R.; Ahn, S.K.; Moon, S.K. Identification of CKD-516: A potent tubulin polymerization inhibitor with marked antitumor activity against murine and human solid tumors. J. Med. Chem., 2010, 53, 6337-6354.
67. Lee, J.; Bae, S.; Lee, S.H.; Choi, H.; Kim, Y.H.; Kim, S.J.; Park, G.T.; Moon, S.K.; Kim, D.H.; Lee, S. Discovery of a potent tubulin polymerization inhibitor: Synthesis and evaluation of water-soluble prodrugs of benzophenone analog. Bioorg. Med. Chem. Lett., 2010, 20, 6327-6330.
68. Kandeel, M.M.; Kamal, A.M.; Abdelall, E.K.; Elshemy, H.A. Synthesis of novel chromene derivatives of expected antitumor activity. Eur. J. Med. Chem., 2013, 59, 183-193.
69. Romagnoli, R.; Baraldi, P.G.; Salvador, M.K.; Prencipe, F.; Bertolasi, V.; Cancellieri, M.; Brancale, A.; Hamel, E.; Castagliuolo, I.; Consolaro, F. Synthesis, Antimitotic and antivascular activity of 1-(3', 4', 5'-Trimethoxybenzoyl)-3-arylamino-5-amino-1, 2, 4- triazoles. J. Med. Chem., 2014, 57, 6795-6808.
70. Wong, E.; Giandomenico, C.M. Current status of platinum-based antitumor drugs. Chem. Rev., 1999, 99, 2451-2466.
71. Jamieson, E.R.; Lippard, S.J., Structure, recognition, and processing of cisplatin-DNA adducts. Chem. Rev.,1999, 99, 2467-2498.
72. Weiss, R.B.; Christian, M.C. New cisplatin analogues in development. Drugs, 1993, 46, 360-377.
73. Al_Masoudi, N.A.; Abdullah, B.H.; Essa, A.H.; Loddo, R.; LaColla, P., Platinum and Palladium_triazole Complexes as Highly Potential Antitumor Agents. Arch. Pharm., 2010, 343, 222-227.
74. Ferrari, M.B.; Gasparri Fava, G.; Leporati, E.; Pelosi, G.; Rossi, R.; Tarasconi, P.; Albertini, R.; Bonati, A.; Lunghi, P.; Pinelli, S. Synthesis, characterisation and biological activity of three copper (II) complexes with a modified nitrogenous base: 5-formyluracil thiosemicarbazone. J. Inorg. Biochem., 1998, 70, 145-154.
75. Chen, D.; Cui, Q.C.; Yang, H.; Dou, Q.P. Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity. Cancer Res., 2006, 66, 10425-10433.
76. Uriu-Adams, J.Y.; Keen, C.L., Copper, oxidative stress and human health. Mol. Aspects Med., 2005, 26, 268-298.
77. Majumder, S.; Panda, G.S.; Kumar Choudhuri, S., Synthesis, characterization and biological properties of a novel copper complex. Eur. J. Med. Chem., 2003, 38, 893-898.
78. Dallavalle, F.; Gaccioli, F.; Franchi-Gazzola, R.; Lanfranchi, M.; Marchio, L.; Pellinghelli, M.A.; Tegoni, M. Synthesis, molecular structure, solution equilibrium, and anti-proliferative activity of thioxotriazoline and thioxotriazole complexes of copper (II) and palladium (II). J. Inorg. Biochem., 2002, 92, 95-104.
79. Tardito, S.; Bussolati, O.; Gaccioli, F.; Gatti, R.; Guizzardi, S.; Uggeri, J.; Marchio, L.; Lanfranchi, M.; Franchi-Gazzola, R. Nonapoptotic programmed cell death induced by a copper (II) complex in human fibrosarcoma cells. Histochem. Cell Biol., 2006, 126, 473-482.
80. Tardito, S.; Bussolati, O.; Maffini, M.; Tegoni, M.; Giannetto, M.; Dall'Asta, V.; Franchi-Gazzola, R.; Lanfranchi, M.; Pellinghelli, M.A.; Mucchino, C., Thioamido coordination in a thioxo-1, 2, 4- triazole copper (II) complex enhances nonapoptotic programmed cell death associated with copper accumulation and oxidative stress in human cancer cells. J. Med. Chem., 2007, 50, 1916-1924.
81. Marzano, C.; Pellei, M.; Colavito, D.; Alidori, S.; Lobbia, G.G.; Gandin, V.; Tisato, F.; Santini, C., Synthesis characterization, and in vitro antitumor properties of tris (hydroxymethyl) phosphine copper (I) complexes containing the new bis (1, 2, 4-triazol-1-yl) acetate ligand. J. Med. Chem., 2006, 49, 7317-7324.
82. O’Dwyer, P.; Stevenson, J.; Johnson, S.; Lippert, B., Cisplatin: Chemistry and biochemistry of a leading anticancer drug. by Lippert B., Wiley-VCH, Weinheim, 1999-3169.
83. Sava, G.; Gagliardi, R.; Bergamo, A.; Alessio, E.; Mestroni, G. Treatment of metastases of solid mouse tumours by NAMI-A: Comparison with cisplatin, cyclophosphamide and dacarbazine. Anticancer Res., 1998, 19, 969-972.
84. Galanski, M.; Arion, V.; Jakupec, M.; Keppler, B. Recent developments in the field of tumor-inhibiting metal complexes. Curr. Pharm. Des., 2003, 9, 2078-2089.
85. Arion, V.B.; Reisner, E.; Fremuth, M.; Jakupec, M.A.; Keppler, B.K.; Kukushkin, V.Y.; Pombeiro, A.J., Synthesis, X-ray diffraction structures, spectroscopic properties, and in vitro Antitumor Activity of Isomeric (1 H-1, 2, 4-Triazole) Ru (III) Complexes. Inorg. Chem., 2003, 42, 6024-6031.
86. Groessl, M.; Reisner, E.; Hartinger, C.G.; Eichinger, R.; Semenova, O.; Timerbaev, A.R.; Jakupec, M.A.; Arion, V.B.; Keppler, B.K. Structure-activity relationships for NAMI-A-type complexes (HL)[trans-RuCl4L (S-dmso) ruthenate (III)](L= imidazole, indazole, 1, 2, 4-triazole, 4-amino-1, 2, 4-triazole, and 1-methyl-1, 2, 4-triazole): aquation, redox properties, protein binding, and antiproliferative activity. J. Med. Chem., 2007, 50, 2185-2193.
87. Serebryanskaya, T.; Zolotarev, A.; Ott, I. A novel aminotriazole-based NHC complex for the design of gold (i) anti-cancer agents: Synthesis and biological evaluation. Med. Chem. Comm., 2015, 6, 1186-1189.
88. Tyagi, P.; Chandra, S.; Saraswat, B.; Yadav, D. Design, spectral characterization, thermal, DFT studies and anticancer cell line activities of Co (II), Ni (II) and Cu (II) complexes of Schiff bases derived from 4-amino-5-(pyridin-4-yl)-4H-1, 2, 4-triazole-3-thiol. Spectrochim. Acta A Mol. Biomol. Spectrosc, 2015, 145, 155-164.
89. Testa, B.; Jenner, P. Inhibitors of cytochrome P-450s and their mechanism of action. Drug Metab. Rev., 1981, 12, 1-117.
90. Bossche, H.V.; Willemsens, G.; Roels, I.; Bellens, D.; Moereels, H.; Coene, M.C.; Jeune, L.L.; Lauwers, W.; Janssen, P.A. R 76713 and enantiomers: Selective, nonsteroidal inhibitors of the cytochrome P450-dependent oestrogen synthesis. Biochem. Pharmacol., 1990, 40, 1707-1718.
91. Wiseman, L.R.; Spencer, C.M. Vorozole. Drugs & aging 1997, 11, 245-50; discussion 251-252.
92. Wouters, W.; Snoeck, E.; De Coster, R. Vorozole, a specific nonsteroidal aromatase inhibitor. Breast Cancer Res. Treat., 1994, 30, 89-94.
93. Wouters, W.; De Coster, R.; Krekels, M.; Van Dun, J.; Beerens, D.; Haelterman, C.; Raeymaekers, A.; Freyne, E.; Van Gelder, J.; Venet, M.R 76713, a new specific non-steroidal aromatase inhibitor. J. Steroid. Biochem. Mol. Biol., 1989, 32, 781-788.
94. Simpson, D.; Curran, M.P.; Perry, C.M. Letrozole: A review of its use in postmenopausal women with breast cancer. Drugs, 2004, 64, 1213-1230.
95. Geisler, J.; King, N.; Dowsett, M.; Ottestad, L.; Lundgren, S.; Walton, P.; Kormeset, P.; Lonning, P.E., Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal women with breast cancer. Br. J. Cancer, 1996, 74, 1286.
96. Plourde, P.V.; Dyroff, M.; Dukes, M. Arimidex®: A potent and selective fourth-generation aromatase inhibitor. Breast Cancer Res. Treat, 1994, 30, 103-111.
97. Okada, M.; Yoden, T.; Kawaminami, E.; Shimada, Y.; Kudoh, M.; Isomura, Y.; Shikama, H.; Fujikura, T., Studies on aromatase inhibitors. I. Synthesis and biological evaluation of 4-amino-4H-1, 2, 4-triazole derivatives. Chem. Pharm. Bull., 1996, 44, 1871-1879.
98. Leze, M.P.; Palusczak, A.; Hartmann, R.W.; Le Borgne, M., Synthesis of 6-or 4-functionalized indoles via a reductive cyclization approach and evaluation as aromatase inhibitors. Bioorg. Med. Chem. Lett., 2008, 18, 4713-4715.
99. Caporuscio, F.; Rastelli, G.; Imbriano, C.; Del Rio, A. Structurebased design of potent aromatase inhibitors by high-throughput docking. J. Med. Chem., 2011, 54, 4006-4017.
100. Yamamoto, T.; Kitawaki, J.; Urabe, M.; Honjo, H.; Tamura, T.; Noguchi, T.; Okada, H.; Sasaki, H.; Tada, A.; Terashima, Y., Estrogen productivity of endometrium and endometrial cancer tissue; influence of aromatase on proliferation of endometrial cancer cells. J. Steroid Biochem. Mol. Biol., 1993, 44, 463-468
101. Bajetta, E.; Zilembo, N.; Bichisao, E.; Martinetti, A.; Buzzoni, R.; Pozzi, P.; Bidoli, P.; Ferrari, L.; Celio, L., Tumor response and estrogen suppression in breast cancer patients treated with aromatase inhibitors. Ann. Oncol., 2000, 11, 1017-1022.
102. Woo, L.L.; Sutcliffe, O.B.; Bubert, C.; Grasso, A.; Chander, S.K.; Purohit, A.; Reed, M.J.; Potter, B.V. First dual aromatase-steroid sulfatase inhibitors. J. Med. Chem., 2003, 46, 3193-3196.
103. Woo, L.L.; Bubert, C.; Sutcliffe, O.B.; Smith, A.; Chander, S.K.; Mahon, M.F.; Purohit, A.; Reed, M.J.; Potter, B.V. Dual aromatase-steroid sulfatase inhibitors. J. Med. Chem., 2007, 50, 3540-3560.
104. Bubert, C.; Woo, L.; Sutcliffe, O.B.; Mahon, M.F.; Chander, S.K.; Purohit, A.; Reed, M.J.; Potter, B.V., Synthesis of aromatase inhibitors and dual aromatase steroid sulfatase inhibitors by linking an arylsulfamate motif to 4_(4H_1, 2, 4_triazol_4_ylamino) benzonitrile: SAR, Crystal structures, in vitro and in vivo Activities. Chem. Med. Chem., 2008, 3, 1708-1730.
105. Wood, P.M.; Woo, L.; Humphreys, A.; Chander, S.K.; Purohit, A.; Reed, M.J.; Potter, B.V. A letrozole-based dual aromatase– sulphatase inhibitor with in vivo activity. J. Steroid. Biochem. Mol. Biol., 2005, 94, 123-130.
106. Wood, P.M.; Woo, L.L.; Labrosse, J.R.; Trusselle, M.N.; Abbate, S.; Longhi, G.; Castiglioni, E.; Lebon, F.; Purohit, A.; Reed, M.J., Chiral aromatase and dual aromatase- steroid sulfatase inhibitors from the letrozole template: Synthesis, absolute configuration, and in Vitro activity. J. Med. Chem. 2008, 51, 4226-4238.
107. Castonguay, A.; Doucet, C.D.; Juhas, M.; Maysinger, D. New Ruthenium (II)-Letrozole Complexes as Anticancer Therapeutics. J. Med. Chem., 2012, 55, 8799-8806.
108. Jackson, T.; Woo, L.L.; Trusselle, M.N.; Chander, S.K.; Purohit, A.; Reed, M.J.; Potter, B.V. Dual aromatase–sulfatase inhibitors based on the anastrozole template: Synthesis, in vitro SAR, molecular modelling and in vivo activity. Org. Biomol. Chem., 2007, 5, 2940-2952.
109. Okada, M.; Nakagawa, T.; Iwashita, S.; Takegawa, S.; Fujii, T.; Koizumi, N. Development of novel steroid sulfatase inhibitors: I. Synthesis and biological evaluation of biphenyl-4-O-sulfamates. J. Steroid. Biochem. Mol. Biol., 2003, 87, 141-148.
110. Woo, L.L.; Jackson, T.; Putey, A.l.; Cozier, G.; Leonard, P.; Acharya, K.R.; Chander, S.K.; Purohit, A.; Reed, M.J.; Potter, B.V., Highly potent first examples of dual aromatase steroid sulfatase inhibitors based on a biphenyl template. J. Med. Chem., 2010, 53, 2155-2170.
111. Woo, L.L.; Bubert, C.; Purohit, A.; Potter, B.V. Hybrid dual aromatase-steroid sulfatase inhibitors with exquisite picomolar inhibitory activity. ACS Med. Chem. Lett., 2010, 2, 243-247.
112. Bey, E.; Marchais-Oberwinkler, S.; Werth, R.; Negri, M.; Al-Soud, Y.A.; Kruchten, P.; Oster, A.; Frotscher, M.; Birk, B.; Hartmann, R.W. Design, synthesis, biological evaluation and pharmacokinetics of bis (hydroxyphenyl) substituted azoles, thiophenes, benzenes, and aza-benzenes as potent and selective nonsteroidal inhibitors of 17ß- hydroxysteroid dehydrogenase type 1 (17ß-HSD1). J. Med. Chem., 2008, 51, 6725-6739.
113. Kawai, M.; BaMaung, N.Y.; Fidanze, S.D.; Erickson, S.A.; Tedrow, J.S.; Sanders, W.J.; Vasudevan, A.; Park, C.; Hutchins, C.; Comess, K.M. Development of sulfonamide compounds as potent methionine aminopeptidase type II inhibitors with anti-proliferative properties. Bioorg. Med. Chem., 2006, 16, 3574-3577.
114. Chang, S.; MCGARY, E.C.; Chang, S., Methionine aminopeptidase gene of Escherichia coli is essential for cell growth. J. Bacteriol., 1989, 171, 4071-4072.
115. Hannig, G.; Lazarus, D.D.; Bernier, S.G.; Karp, R.M.; Lorusso, J.; Qiu, D.; Labenski, M.T.; Wakefield, J.D.; Thompson, C.D.; Westlin, W.F. Inhibition of melanoma tumor growth by a pharmacological inhibitor of MetAP-2, PPI-2458. Int. J. Oncol., 2006, 28, 955-963.
116. Marino, J.P.; Fisher, P.W.; Hofmann, G.A.; Kirkpatrick, R.B.; Janson, C.A.; Johnson, R.K.; Ma, C.; Mattern, M.; Meek, T.D.; Ryan, M.D. Highly potent inhibitors of methionine aminopeptidase-2 based on a 1, 2, 4-triazole pharmacophore. J. Med. Chem., 2007, 50, 3777-3785.
117. Hou, Y.-P.; Sun, J.; Pang, Z.-H.; Lv, P.-C.; Li, D.-D.; Yan, L.; Zhang, H.-J.; Zheng, E.X.; Zhao, J.; Zhu, H.L., Synthesis and antitumor activity of 1, 2, 4-triazoles having 1, 4-benzodioxan fragment as a novel class of potent methionine aminopeptidase type II inhibitors. Bioorg. Med. Chem., 2011, 19, 5948-5954.
118. He, Q.J.; Yang, B.; Lou, Y.J.; Fang, R.Y., Contragestazol (DL111_IT) inhibits proliferation of human an_drogen_independent prostate cancer cell line PC3 in vitro and in vivo. Asi. J. Androl., 2005, 7, 389-393.
119. Galliani, G.; Luzzani, F.; Colombo, G.; Conz, A.; Mistrello, L.; Barone, D.; Lancini, G.; Assandri, A. On the mode of action of a new contragestational agent (DL 111-IT). Contraception, 1986, 33, 263-283.
120. Yang Bo, C.L.; Ruiying, F.; Zhiping, G. Luteolytic effects of DL111-IT in pregnant rats. Eur. J. Pharmacol., 1999, 380, 145-152.
121. Assandri, A.; Perazzi, A.; Omodei-Salé, A.; Sartori, G.; Galliani, G. Pharmacokinetics-activity relationships of a new non-hormonal antifertility agent: 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1, 2, 4-triazole, in the rat and the hamster. Eur. J. Drug Metab. Pharmacokinet., 1983, 8, 9-16.
122. Yang, B.; He, Q.J.; Zhu, D.Y.; Lou, Y.J.; Fang, R.Y., Antiproliferative activity of contragestazol (DL111-IT) in murine and human tumor models in vitro and in vivo. Cancer Chemother. Pharmacol., 2006, 57, 268-273.
123. Loiarro, M.; Campo, S.; Arseni, B.; Rossi, S.; D'Alessio, V.; De Santis, R.; Sette, C.; Ruggiero, V. Anti_proliferative effect of a triazole derivative (ST1959) on LNCaP human prostate cancer cells through down_regulation of cyclin and androgen receptor expression. The Prostate, 2011, 71, 32-41.
124. Huang, S.M.A.; Mishina, Y.M.; Liu, S.; Cheung, A.; Stegmeier, F.; Michaud, G.A.; Charlat, O.; Wiellette, E.; Zhang, Y.; Wiessner, S. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature, 2009, 461, 614-620.
125. Waaler, J.; Machon, O.; Von Kries, J.P.; Wilson, S.R.; Lundenes, E.; Wedlich, D.; Gradl, D.; Paulsen, J.E.; Machonova, O.; Dembinski, J.L. Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth. Cancer Res., 2011, 71, 197-205.
126. Voronkov, A.; Holsworth, D.D.; Waaler, J.; Wilson, S.R.; Ekblad, B.; Perdreau-Dahl, H.; Dinh, H.; Drewes, G.; Hopf, C.; Morth, J.P., Structural basis and SAR for G007-LK, a lead stage 1, 2, 4-triazole based specific tankyrase 1/2 inhibitor. J. Med. Chem., 2013, 56, 3012-3023.
127. Shultz, M.D.; Kirby, C.A.; Stams, T.; Chin, D.N.; Blank, J.; Charlat, O.; Cheng, H.; Cheung, A.; Cong, F.; Feng, Y. [1, 2, 4] Triazol-3-ylsulfanylmethyl-3-phenyl-[1, 2, 4] oxadiazoles: Antagonists of the Wnt pathway that inhibit tankyrases 1 and 2 via novel adenosine pocket binding. J. Med. Chem., 2012, 55, 1127-1136.
128. Demirbas, N.; Karaoglu, S.A.; Demirbas, A.; Sancak, K. Synthesis and antimicrobial activities of some new 1-(5-phenylamino-[1, 3, 4] thiadiazol-2-yl) methyl-5-oxo-[1, 2, 4] triazole and 1-(4-phenyl- 5-thioxo-[1, 2, 4] triazol-3-yl) methyl-5-oxo-[1, 2, 4] triazole derivatives. Eur. J. Med. Chem., 2004, 39, 793-804.
129. Li, Z.; Gu, Z.; Yin, K.; Zhang, R.; Deng, Q.; Xiang, J., Synthesis of substituted-phenyl-1, 2, 4-triazol-3-thione analogues with modified d-glucopyranosyl residues and their anti-proliferative activities. Eur. J. Med. Chem., 2009, 44, 4716-4720.
130. Arafa, R.K.; Hegazy, G.H.; Piazza, G.A.; Abadi, A.H., Synthesis and in vitro anti-proliferative effect of novel quinoline-based potential anticancer agents. Eur. J. Med. Chem., 2013, 63, 826-832.
131. Corona, P.; Vitale, G.; Loriga, M.; Paglietti, G.; La Colla, P.; Collu, G.; Sanna, G.; Loddo, R. 4-Substituted anilino imidazo [1, 2-a] and triazolo [4, 3-a] quinoxalines. Synthesis and evaluation of in vitro biological activity. Eur. J. Med. Chem., 2006, 41, 1102-1107.
132. Kamal, A.; Khan, M.N.A.; Reddy, K.S.; Srikanth, Y.; Sridhar, B., Synthesis, structural characterization and biological evaluation of novel [1, 2, 4] triazolo [1, 5 b][1, 2, 4] benzothiadiazine_benzothiazole conjugates as potential anticancer agents. Chem. Biol. Drug Des., 2008, 71, 78-86.
133. Sztanke, K.; Tuzimski, T.; Rzymowska, J.; Pasternak, K.; Kandefer-Szerszen, M. Synthesis, determination of the lipophilicity, anticancer and antimicrobial properties of some fused 1, 2, 4-triazole derivatives. Eur. J. Med. Chem., 2008, 43, 404-419.
134. Zhang, C.; Li, W. Regioselective synthesis of 6-aryl-benzo[h] [1,2,4]-triazolo[5,1-b]quinazoline-7,8-diones as potent antitumoral agents. Bioorg. Med. Chem. Lett., 2013, 23, 5002-5005.
135. Kamal, A.; Khan, M.N.A.; Srikanth, Y.; Srinivasa Reddy, K.; Juvekar, A.; Sen, S.; Kurian, N.; Zingde, S. Synthesis, DNAbinding ability and evaluation of antitumour activity of triazolo [1,2,4]benzothiadiazine linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates. Bioorg. Med. Chem., 2008, 16, 7804-7810.
136. Bhat, K.S.; Poojary, B.; Prasad, D.J.; Naik, P.; Holla, B.S. Synthesis and antitumor activity studies of some new fused 1, 2, 4- triazole derivatives carrying 2, 4-dichloro-5-fluorophenyl moiety. Eur. J. Med. Chem., 2009, 44, 5066-5070.
137. Allen, J.G.; Bourbeau, M.P.; Wohlhieter, G.E.; Bartberger, M.D.; Michelsen, K.; Hungate, R.; Gadwood, R.C.; Gaston, R.D.; Evans, B.; Mann, L.W., Discovery and optimization of chromenotriazolopyrimidines as potent inhibitors of the mouse double minute 2- tumor protein 53 protein- protein interaction. J. Med. Chem., 2009, 52, 7044-7053.
138. Ilango, K.; Valentina, P., Facile synthesis and cytotoxic activity of 3, 6-disubstituted 1, 2, 4-triazolo-[3, 4-b]-1, 3, 4-thiadiazoles. Eur J. Chem., 2010, 1, 50-53.
139. Bradbury, R.H.; Hales, N.J.; Rabow, A.A.; Walker, G.E.; Acton, D.G.; Andrews, D.M.; Ballard, P.; Brooks, N.A.; Colclough, N.; Girdwood, A. Small-molecule androgen receptor downregulators as an approach to treatment of advanced prostate cancer. Bioorg. Med. Chem. Lett., 2011, 21, 5442-5445.
140. Muralikrishna, A.; Venkatesh, B.; Padmavathi, V.; Padmaja, A.; Kondaiah, P.; Krishna, N.S., Synthesis, antimicrobial and cytotoxic activities of sulfone linked bis heterocycles. Eur. J. Med. Chem., 2012, 54, 605-614.
141. Husain, A.; Rashid, M.; Mishra, R.; Parveen, S.; Shin, D.S.; Kumar, D., Benzimidazole bearing oxadiazole and triazolothiadiazoles nucleus: Design and synthesis as anticancer agents. Bioorg. Med. Chem. Lett., 2012, 22, 5438-5444.
142. Rashid, M.; Husain, A.; Siddiqui, A.A.; Mishra, R. Benzimidazole clubbed with triazolo-thiadiazoles and triazolo-thiadiazines: New anticancer agents. Eur. J. Med. Chem., 2013, 62, 785-798.
143. Sumangala, V.; Poojary, B.; Chidananda, N.; Arulmoli, T.; Shenoy, S., Facile synthesis, cytotoxic and antimicrobial activity studies of a new group of 6-aryl-3-[4-(methylsulfonyl)benzyl]-7H-[1,2,4]triazolo [3,4-b][1,3,4]thiadiazines. Eur. J. Med. Chem., 2012, 54, 59-64.
144. Puthiyapurayil, P.; Poojary, B.; Chikkanna, C.; Buridipad, S.K., Synthesis spectral characterization and biological evaluation of a novel series of 6-arylsubstituted-3-[2-(4-substitutedphenyl)propan- 2-yl]-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines Eur. J. Med.. Chem., 2012, 57, 407-416.
145. Laura Almajan, G.; Innocenti, A.; Puccetti, L.; Manole, G.; Barbuceanu, S.; Saramet, I.; Scozzafava, A.; Supuran, C.T. Carbonic anhydrase inhibitors. Inhibition of the cytosolic and tumor-associated carbonic anhydrase isozymes I, II, and IX with a series of 1, 3, 4-thiadiazole-and 1, 2, 4-triazole-thiols. Bioorg. Med. Chem. Lett., 2005, 15, 2347-2352.
146. Potter, C.H.A.L. Hypoxia inducible carbonic anhydrase IX, marker of tumour hypoxia, survival pathway and therapy target. Cell Cycle, 2004, 3, 164-167.
147. Robertson, N.P.C.; Harris, A. L. Role of carbonic anhydrase IX in human tumor cell growth, survival, and invasion. Cancer Res., 2004, 64, 6160-6165.
148. SitaRam Celik, G.; Khloya, P.; Vullo, D.; Supuran, C.T.; Sharma, P.K., Benzenesulfonamide bearing 1,2,4-triazole scaffolds as potent inhibitors of tumor associated carbonic anhydrase isoforms hCA IX and hCA XII. Bioorg. Med. Chem., 2014, 22, 1873-1882.
149. Holla, B.S.; Sarojini, B.K.; Rao, B.S.; Akberali, P.M.; Kumari, N.S.; Shetty, V. Synthesis of some halogen-containing 1, 2, 4- triazolo-1, 3, 4-thiadiazines and their antibacterial and anticancer screening studies-Part I. Il Farmaco, 2001, 56, 565-570.
150. Holla, B.S.; Poojary, K.N.; Rao, B.S.; Shivananda, M.K., New bisaminomercaptotriazoles and bis-triazolothiadiazoles as possible anticancer agents. Eur. J. Med. Chem., 2002, 37, 511-517.
151. Shivarama Holla, B.; Sooryanarayana Rao, B.; Sarojini, B.; Akberali, P.; Suchetha Kumari, N. Synthesis and studies on some new fluorine containing triazolothiadiazines as possible antibacterial, antifungal and anticancer agents. Eur. J. Med. Chem., 2006, 41, 657-663.
152. Shivarama Holla, B.; Veerendra, B.; Shivananda, M.; Poojary, B., Synthesis characterization and anticancer activity studies on some Mannich bases derived from 1, 2, 4-triazoles. Eur. J. Med. Chem., 2003, 38, 759-767.
153. Pomarnacka, E.; Gdaniec, M., Synthesis and anticancer activity of 2-amino-8-chloro-5,5-dioxo[1,2,4]triazolo[2,3-b][1,4,2]benzodithiazine derivatives. Bioorg. Med. Chem., 2003, 11, 1259-1267.
154. Rostom, S.A.; Shalaby, M.A.; El-Demellawy, M.A. Polysubstituted pyrazoles, part 5. Synthesis of new 1-(4-chlorophenyl)-4-hydroxy- 1H-pyrazole-3-carboxylic acid hydrazide analogs and some derived ring systems. A novel class of potential antitumor and anti-HCV agents. Eur. J. Med. Chem., 2003, 38, 959-974.
155. Lesyk, R.; Vladzimirska, O.; Holota, S.; Zaprutko, L.; Gzella, A. New 5-substituted thiazolo[3,2-b][1,2,4]triazol-6-ones: Synthesis and anticancer evaluation. Eur. J. Med. Chem., 2007, 42, 641-648.
156. Mavrova, A.T.; Wesselinova, D.; Tsenov, Y.A.; Denkova, P. Synthesis, cytotoxicity and effects of some 1, 2, 4-triazole and 1, 3, 4-thiadiazole derivatives on immunocompetent cells. Eur. J. Med. Chem., 2009, 44, 63-69.
157. Pachuta-Stec, A.; Rzymowska, J.; Mazur, L.; Mendyk, E.; Pitucha, M.; Rzaczynska, Z. Synthesis, structure elucidation and antitumour activity of N-substituted amides of 3-(3-ethylthio-1,2,4-triazol-5- yl)propenoic acid. Eur. J. Med. Chem., 2009, 44, 3788-3793.
158. Zhang, Y.B.; Wang, X.L.; Liu, W.; Yang, Y.S.; Tang, J.F.; Zhu, H.L., Design, synthesis and biological evaluation of heterocyclic azoles derivatives containing pyrazine moiety as potential telomerase inhibitors. Bioorg. Med. Chem., 2012, 20, 6356-6365.
159. Tanushree Singha, J.S.; Arup, N.; Tirtha, G.; Arijit, M.; Mrityunjoy, K.; Ranjit, K.H.; Tapan, K.M., Synthesis and Evaluation of Anti-proliferative activity of 1, 2, 4-Triazole Derivatives Against EAC Bearing Mice Model Ind. J. Pharm. Edu. Res., 2012, 46(4), 346-351.
160. Zhao, P.L.; Ma, W.F.; Duan, A.N.; Zou, M.; Yan, Y.C.; You, W.W.; Wu, S.G., One-pot synthesis of novel isoindoline-1, 3-dione derivatives bearing 1, 2, 4-triazole moiety and their preliminary biological evaluation. Eur. J. Med. Chem., 2012, 54, 813-822.
161. Zhao, P.L.; Duan, A.N.; Zou, M.; Yang, H.K.; You, W.W.; Wu, S.G. Synthesis and cytotoxicity of 3,4-disubstituted-5-(3,4,5- trimethoxyphenyl)-4H-1,2,4-triazoles and novel 5,6-dihydro- [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives bearing 3,4,5- trimethoxyphenyl moiety. Bioorg. Med. Chem. Lett., 2012, 22, 4471-4474.
162. Abdel-Aziz, M.; Abuo-Rahma, G.E.D.A.; Beshr, E.A.; Ali, T.F. New Nitric Oxide Donating 1, 2, 4-Triazole/Oxime Hybrids: Synthesis, investigation of anti-inflammatory, ulceroginic liability and anti-proliferative activities. Bioorg. Med. Chem., 2013, 21, 3839-3849.
163. Abuo-Rahma, G.E.D.A.; Abdel-Aziz, M.; Beshr, E.A.; Ali, T.F. 1, 2, 4-Triazole/oxime hybrids as new strategy for nitric oxide donors: Synthesis, anti-inflammatory, ulceroginicity and anti-proliferative activities. Eur. J. Med. Chem., 2014, 71, 185-198.
164. Hamdy, R.; Ziedan, N.; Ali, S.; El-Sadek, M.; Lashin, E.; Brancale, A.; Jones, A.T.; Westwell, A.D., Synthesis and evaluation of 3- (benzylthio)-5-(1H-indol-3-yl)-1,2,4-triazol-4-amines as Bcl-2 inhibitory anticancer agents. Bioorg. Med. Chem. Lett., 2013, 23, 2391-2394.
165. Hassan, G.S.; El-Messery, S.M.; Al-Omary, F.A.; Al-Rashood, S.T.; Shabayek, M.I.; Abulfadl, Y.S.; Habib, E.S.E.; El-Hallouty, S.M.; Fayad, W.; Mohamed, K.M. Nonclassical antifolates, part 4. 5-(2-Aminothiazol-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiols as a new class of DHFR inhibitors: Synthesis, biological evaluation and molecular modeling study. Eur. J. Med. Chem., 2013, 66, 135-145.
166. Hunt, J.T.; Ding, C.Z.; Batorsky, R.; Bednarz, M.; Bhide, R.; Cho, Y.; Chong, S.; Chao, S.; Gullo-Brown, J.; Guo, P. Discovery of (R)-7-cyano-2, 3, 4, 5-tetrahydro-1-(1 H-imidazol-4-ylmethyl)-3- (phenylmethyl)-4-(2-thienylsulfonyl)-1 H-1, 4-benzodiazepine (BMS-214662), a farnesyltransferase inhibitor with potent preclinical antitumor activity. J. Med. Chem., 2000, 43, 3587-3595.
167. Saha, A.K.; Liu, L.; Simoneaux, R.; DeCorte, B.; Meyer, C.; Skrzat, S.; Breslin, H.J.; Kukla, M.J.; End, D.W. Novel triazole based inhibitors of Ras farnesyl transferase. Bioorg. Med. Chem. Lett., 2005, 15, 5407-5411.
168. Bekircan, O.; Kahveci, B.; Kucuk, M., Synthesis and anticancer evaluation of some new unsymmetrical 3, 5-diaryl-4H-1, 2, 4- triazole derivatives. Turk. J. Chem., 2006, 30, 29-40.
169. Pautus, S.; Yee, S.W.; Jayne, M.; Coogan, M.P.; Simons, C., Synthesis and CYP26A1 inhibitory activity of 1-[benzofuran-2-yl- (4-alkyl/aryl-phenyl)-methyl]-1H-triazoles. Bioorg. Med. Chem., 2006, 14, 3643-3653.
170. Gomaa, M.S.; Armstrong, J.L.; Bobillon, B.; Veal, G.J.; Brancale, A.; Redfern, C.P.; Simons, C. Novel azolyl-(phenylmethyl)] aryl/heteroarylamines: Potent CYP26 inhibitors and enhancers of all-trans retinoic acid activity in neuroblastoma cells. Bioorg. Med. Chem., 2008, 16, 8301-8313.
171. Eiznhamer, D.; Xu, Z. Betulinic acid: A promising anticancer candidate. Invest. New Drug, 2004, 7, 359.
172. Mukherjee, R.; Kumar, V.; Srivastava, S.K.; Agarwal, S.K.; Burman, A.C. Betulinic acid derivatives as anticancer agents: Structure activity relationship. Curr. Med. Chem.: Anti-Cancer Agents, 2006, 6, 271-279.
173. Santos, R.C.; Salvador, J.A.; Marín, S.; Cascante, M.; Moreira, J.N.; Dinis, T.C. Synthesis and structure–activity relationship study of novel cytotoxic carbamate and N-acylheterocyclic bearing derivatives of betulin and betulinic acid. Bioorg. Med. Chem., 2010, 18, 4385-4396.
174. Ozkay, Y.; Isikdag, I.; Incesu, Z.; Akalin, G., Synthesis of 2- substituted-N-[4-(1-methyl-4,5-diphenyl-1H-imidazole-2- yl)phenyl]acetamide derivatives and evaluation of their anticancer activity. Eur. J. Med. Chem., 2010, 45, 3320-3328.
175. Derevkova, V.; Balalaeva, I.; Papina, R.; Korepin, A.; Glushakova, N.; Terent’ev, A., Cytostatic action of triazole and oxazolidinone derivatives. Russ. Chem. Bull., 2011, 60, 1166-1171.
176. Wang, L.Y.; Tseng, W.C.; Wu, T.S.; Kaneko, K.; Takayama, H.; Kimura, M.; Yang, W.C.; Wu, J.B.; Juang, S.H.; Wong, F.F. Synthesis and anti-proliferative evaluation of 3, 5-disubstituted 1, 2, 4-triazoles containing flurophenyl and trifluoromethanephenyl moieties. Bioorg. Med. Chem. Lett., 2011, 21, 5358-5362.
177. Ibrahim, M.A.; Johnson, H.W.; Jeong, J.W.; Lewis, G.L.; Shi, X.; Noguchi, R.T.; Williams, M.; Leahy, J.W.; Nuss, J.M.; Woolfrey, J., Discovery of a novel class of potent and orally bioavailable sphingosine 1-phosphate receptor 1 antagonists. J. Med. Chem., 2012, 55, 1368-1381.
178. Wittine, K.; Stipkovic Babic, M.; Makuc, D.; Plavec, J.; Kraljevic Pavelic, S.; Sedic, M.; Pavelic, K.; Leyssen, P.; Neyts, J.; Balzarini, J. Novel 1, 2, 4-triazole and imidazole derivatives of L-ascorbic and imino-ascorbic acid: Synthesis, anti-HCV and antitumor activity evaluations. Bioorg. Med. Chem. Lett., 2012, 20, 3675-3685.
179. Leal, A.S.; Wang, R.; Salvador, J.A.; Jing, Y. Synthesis of novel ursolic acid heterocyclic derivatives with improved abilities of antiproliferation and induction of p53, p21waf1 and NOXA in pancreatic cancer cells. Bioorg. Med. Chem., 2012, 20, 5774-5786.
180. Firas Abdullah Hassan, K.W.Y.A.A.H.A. QaisiAntitumoral effect of 1, 2, 4-Triazole derivatives on prostate carcinoma (DU145), human liver carcinoma (HEPG2), and human breast cancer (MCF7) cell Lines. Aust. J. Basic Appl. Sci., 2013, 7, 133-140.
181. Salerno, L.; Pittala, V.; Romeo, G.; Modica, M.N.; Siracusa, M.A.; Di Giacomo, C.; Acquaviva, R.; Barbagallo, I.; Tibullo, D.; Sorrenti, V. evaluation of novel aryloxyalkyl derivatives of imidazole and 1, 2, 4-triazole as heme oxygenase-1 (HO-1) inhibitors and their antitumor properties. Bioorg. Med. Chem., 2013, 21, 5145-5153.
182. Cristalli, G.; Eleuteri, A.; Volpini, R.; Vittori, S.; Camaioni, E.; Lupidi, G. Adenosine deaminase inhibitors: Synthesis and structure-activity relationships of 2-hydroxy-3-nonyl derivatives of azoles. J. Med. Chem., 1994, 37, 201-205.
183. Al-Soud, Y.A.; Al-Masoudi, N.A.; Ferwanah, A.E.R.S., Synthesis and properties of new substituted 1, 2, 4-triazoles: potential antitumor agents. Bioorg. Med. Chem., 2003, 11, 1701-1708.
184. Ahmad, A.; Varshney, H.; Rauf, A.; Sherwani, A.; Owais, M. Synthesis and anticancer activity of long chain substituted 1, 3, 4- oxadiazol-2-thione, 1, 2, 4-triazol-3-thione and 1, 2, 4-triazolo [3, 4-b]-1, 3, 4-thiadiazine derivatives. Arab. J. Chem., 2014.
185. Qin, M.; Zhai, X.; Xie, H.; Ma, J.; Lu, K.; Wang, Y.; Wang, L.; Gu, Y.; Gong, P., Design and synthesis of novel 2-(4-(2- (dimethylamino) ethyl)-4H-1, 2, 4-triazol-3-yl) pyridines as potential antitumor agents. Eur. J. Med. Chem., 2014, 81, 47-58.
186. Kamel, M.M.; Abdo, N.Y.M., Synthesis of novel 1, 2, 4-triazoles, triazolothiadiazines and triazolothiadiazoles as potential anticancer agents. Eur. J. Med. Chem., 2014, 86, 75-80.
187. Xue, D.Q.; Zhang, X.Y.; Wang, C.J.; Ma, L.Y.; Zhu, N.; He, P.; Shao, K.P.; Chen, P.J.; Gu, Y.F.; Zhang, X.S., Synthesis and anticancer activities of novel 1, 2, 4-triazolo [3, 4-a] phthalazine derivatives. Eur. J. Med. Chem., 2014, 85, 235-244.
188. Mavrova, A.T.; Wesselinova, D.; Tsenov, J.A.; Lubenov, L.A. Synthesis and anti-proliferative activity of some new thieno [2, 3-d] pyrimidin-4 (3H)-ones containing 1, 2, 4-triazole and 1, 3, 4- thiadiazole moiety. Eur. J. Med. Chem., 2014, 86, 676-683.
189. Megally Abdo, N.Y.; Kamel, M.M. Synthesis and Anticancer Evaluation of 1, 3, 4-Oxadiazoles, 1, 3, 4-Thiadiazoles, 1, 2, 4-Triazoles and mannich bases. Chem. Pharm. Bull., 2015, 63, 369-376.
190. Bhat, M.A.; Al-Omar, M.A.; Naglah, A.M.; Abdulla, M.M.; Fun, H.K., Synthesis and antitumor activity of 4-cyclohexyl/aryl-5- (pyridin-4-yl)-2, 4-dihydro-3H-1, 2, 4-triazole-3-thiones. Med. Chem. Res., 2014, 24, 1558-1567.
191. Murty, M.; Ram, K.R.; Rao, B.R.; Rao, R.V.; Katiki, M.R.; Rao, J.V.; Pamanji, R.; Velatooru, L. Synthesis, characterization, and anticancer studies of S and N alkyl piperazine-substituted positional isomers of 1, 2, 4-triazole derivatives. Med. Chem. Res., 2014, 23, 1661-1671.