Chloroquine-based hybrid molecules as promising novel chemotherapeutic agents

European Journal of Pharmacology

Volumn 762, Issue , 2015, Pages 472-486

  Srivastava, Vandana ^a,b   Lee, Hoyun ^a,b  

^a Advanced Medical Research Institute of Canada   (Canada)

^b NORTHERN ONTARIO SCHOOL OF MEDICINE   (Canada)

Author keywords

Artemisinin (PubChem CID: 68827); Chemical compounds studied in this article Chloroquine (PubChem CID: 2719); NSC7092257 (PubChem CID: 398939); SGI 1027 (PubChem CID: 24858111)

Indexed keywords

4 AMINOQUINOLINE ARYL HETEROARYL UREA HYBRID; 4 AMINOQUINOLINE CHALCONE HYBRID; ANTIMALARIAL AGENT; ANTINEOPLASTIC AGENT; CHLOROQUINE; CHLOROQUINE 2,6 DIAMINOPYRIMIDINE HYBRID; CHLOROQUINE ARTEMISININ HYBRID; CHLOROQUINE CHALCONE HYBRID; CHLOROQUINE DIHYDROARTEMISININ HYBRID; CHLOROQUINE DNA ALKYLATING AGENT HYBRID; CHLOROQUINE FERROCENE HYBRID; CHLOROQUINE HETEROCYCLIC SCAFFOLD HYBRID; CHLOROQUINE ISATIN HYBRID; CHLOROQUINE KETOENAMINE CHALCONE HYBRID; CHLOROQUINE ORGANOMETALLIC COMPLEX HYBRID; CHLOROQUINE SULFONAMIDE HYBRID; EPIDERMAL GROWTH FACTOR RECEPTOR; ESTRAMUSTINE; HEMATIN; N CINNAMOYL CHLOROQUINE HYBRID; NLCQ 1; PACLITAXEL; PROTEIN TYROSINE KINASE; UNCLASSIFIED DRUG;

ANTIMALARIAL ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ANTIPROTOZOAL ACTIVITY; DRUG ACCUMULATION; DRUG BIOAVAILABILITY; DRUG CLASSIFICATION; DRUG CYTOTOXICITY; DRUG DNA BINDING; DRUG EFFICACY; DRUG POTENCY; DRUG REPOSITIONING; DRUG RESEARCH; DRUG SAFETY; DRUG SCREENING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; MALARIA CONTROL; MOLECULAR HYBRIDIZATION; NONHUMAN; PHARMACOPHORE; PHASE 2 CLINICAL TRIAL (TOPIC); PLASMODIUM BERGHEI; PLASMODIUM FALCIPARUM; PLASMODIUM VINCKEI; PRIORITY JOURNAL; REVIEW; STRUCTURE ACTIVITY RELATION; CHEMISTRY; DRUG DEVELOPMENT; PROCEDURES;

ANTIMALARIALS; ANTINEOPLASTIC AGENTS; CHLOROQUINE; DRUG DISCOVERY; HUMANS;

EID: 84936858416     PISSN: 00142999     EISSN: 18790712     Source Type: Journal    
DOI: 10.1016/j.ejphar.2015.04.048     Document Type: Review

References (98)

1. K. Abouzid, and S. Shouman Design, synthesis and in vitro antitumor activity of 4-aminoquinoline and 4-aminoquinazoline derivatives targeting EGFR tyrosine kinase Bioorg. Med. Chem. 16 2008 7543 7551 10.1016/j.bmc.2008.07.038
2. Y.C. Acevedo-Morantes, E. Melendez, S.P. Singh, and J.E. Ramírez-Vick Cytotoxicity and reactive oxygen species generated by ferrocenium and ferrocene on MCF7 and MCF10A cell lines J. Cancer Sci. Ther. 04 2012 271 275 10.4172/1948-5956.1000154
3. O.M. Adegbolagun, O.O. Olajuyigbe, O.J. Kazzim, and O. Osho In vitro activity of chloroquine phosphate on the antibacterial potency of ciprofloxacin hydrochloride on the clinical isolates of some gram-negative microorganisms J. Biol. Environ. Sci 2 2008 29 34
4. C. Biot, F. Nosten, L. Fraisse, D. Ter-Minassian, J. Khalife, and D. Dive The antimalarial ferroquine: from bench to clinic Parasite 18 2011 207 214
5. E.C. Breen, and J.J. Walsh Tubulin-targeting agents in hybrid drugs Curr. Med. Chem. 17 2010 609 639
6. P.C.A. Bruijnincx, and P.J. Sadler New trends for metal complexes with anticancer activity Curr. Opin. Chem. Biol. 12 2008 197 206 10.1016/j.cbpa.2007.11.013
7. L. Brulikova, J. Hlavac, and P. Hradil DNA interstrand cross-linking agents and their chemotherapeutic potential Curr. Med. Chem. 19 2012 364 385
8. T.F. Byrd, and M.A. Horwitz Chloroquine inhibits the intracellular multiplication of Legionella pneumophila by limiting the availability of Iron. A potential new mechanism for the therapeutic effect of chloroquine against intracellular pathogens J. Clin. Invest. 88 1991 351 357
9. A. Casini, A. Scozzafava, A. Mastrolorenzo, and L.T. Supuran Sulfonamides and sulfonylated derivatives as anticancer agents Curr. Cancer Drug Targets 2 2002 55 75
10. J. Chadwick, A.E. Mercer, B.K. Park, R. Cosstick, and P.M. O'Neill Synthesis and biological evaluation of extraordinarily potent C-10 carba artemisinin dimers against P. falciparum malaria parasites and HL-60 cancer cells Bioorg. Med. Chem. 17 2009 1325 1338 10.1016/j.bmc.2008.12.017
11. S.S. Chauhan, M. Sharma, and P.M.S. Chauhan Trioxaquines: hybrid molecules for the treatment of malaria Drug News Perspect. 23 2010 632 646 10.1358/dnp.2010.23.10.1468390
12. K. Chibale, I. Ojima, H. Haupt, X. Geng, P. Pera, and R.J. Bernacki Modulation of human mammary cell sensitivity to paclitaxel by new quinoline sulfonamides Bioorg. Med. Chem. Lett. 11 2001 2457 2460 10.1016/S0960-894X(01)00462-0
13. I. Chiyanzu, C. Clarkson, P.J. Smith, J. Lehman, J. Gut, P.J. Rosenthal, and K. Chibale Design, synthesis and anti-plasmodial evaluation in vitro of new 4-aminoquinoline isatin derivatives Bioorg. Med. Chem. 13 2005 3249 3261 10.1016/j.bmc.2005.02.037
14. N.J. Conan Treatment of amebic hepatitis with chloroquine Bull N Y Acad Med 24 1948 545 546
15. N. Costedoat-Chalumeau, B. Dunogué, N. Morel, V. Le Guern, and G. Guettrot-Imbert Hydroxychloroquine: a multifaceted treatment in lupus Presse Med. 43 2014 e167-80 doi:10.1016/j.lpm.2014.03.007
16. J. Datta, K. Ghoshal, W.A. Denny, S.A. Gamage, D.G. Brooke, P. Phiasivongsa, S. Redkar, and S.T. Jacob A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation Cancer Res. 69 2009 4277 4285 10.1158/0008-5472.CAN-08-3669
17. N.B. De Souza, A.M.L. Carmo, D.C. Lagatta, M.J.M. Alves, A.P.S. Fontes, E.S. Coimbra, A.D. da Silva, and C. Abramo 4-Aminoquinoline analogues and its platinum (II) complexes as antimalarial agents Biomed. Pharmacother. 65 2011 313 316 10.1016/j.biopha.2011.03.003
18. W. Engen, T.E. O'Brien, B. Kelly, J. Do, L. Rillera, L.K. Stapleton, J.F. Youngren, and M.O. Anderson Synthesis of aryl-heteroaryl ureas (AHUs) based on 4-aminoquinoline and their evaluation against the insulin-like growth factor receptor (IGF-1R) Bioorg. Med. Chem. 18 2010 5995 6005 10.1016/j.bmc.2010.06.071
19. C. Erlichman, M. Hidalgo, J.P. Boni, P. Martins, S.E. Quinn, C. Zacharchuk, P. Amorusi, A.a. Adjei, and E.K. Rowinsky Phase I study of EKB-569, an irreversible inhibitor of the epidermal growth factor receptor, in patients with advanced solid tumors J. Clin. Oncol. 24 2006 2252 2260 10.1200/JCO.2005.01.8960
20. A. Esparza-Ruiz, C. Herrmann, J. Chen, B.O. Patrick, E. Polishchuk, and C. Orvig Synthesis and in vitro anticancer activity of ferrocenyl-aminoquinoline-carboxamide conjugates Inorg. Chim. Acta 393 2012 276 283 10.1016/j.ica.2012.06.039
21. R. Ferrer, G. Lobo, N. Gamboa, J. Rodrigue, A. Claudia, K. Jung, M. Lein, and J.E. Charris Synthesis of [(7-chloroquinolin-4-yl)amino]chalcones: potential antimalarial and anticancer agents Sci. Pharm. 77 2009 725 741 10.3797/scipharm.0905-07
22. S. Fortin, and G. Bérubé Advances in the development of hybrid anticancer drugs Expert Opin. Drug Discov. 8 2013 1029 1047 10.1517/17460441.2013.798296
23. A.M. Galal, W. Gul, D. Slade, S.a. Ross, S. Feng, M.G. Hollingshead, M.C. Alley, G. Kaur, and M.a. ElSohly Synthesis and evaluation of dihydroartemisinin and dihydroartemisitene acetal dimers showing anticancer and antiprotozoal activity Bioorg. Med. Chem. 17 2009 741 751 10.1016/j.bmc.2008.11.050
24. L.K. Gediya, and V.C. Njar Promise and challenges in drug discovery and development of hybrid anticancer drugs Expert Opin. Drug Discov. 4 2009 1099 1111 10.1517/17460440903341705
25. G.F. Gensini, A.A. Conti, and D. Lippi The contributions of Paul Ehrlich to infectious disease J. Infect. 54 2007 221 224 10.1016/j.jinf.2004.05.022
26. E.M. Guantai, K. Ncokazi, T.J. Egan, J. Gut, P.J. Rosenthal, R. Bhampidipati, A. Kopinathan, P.J. Smith, and K. Chibale Enone- and chalcone-chloroquinoline hybrid analogues: in silico guided design, synthesis, antiplasmodial activity, in vitro metabolism, and mechanistic studies J. Med. Chem. 54 2011 3637 3649 10.1021/jm200149e
27. E.M. Guantai, K. Ncokazi, T.J. Egan, J. Gut, P.J. Rosenthal, P.J. Smith, and K. Chibale Design, synthesis and in vitro antimalarial evaluation of triazole-linked chalcone and dienone hybrid compounds Bioorg. Med. Chem. 18 2010 8243 8256 10.1016/j.bmc.2010.10.009
28. F.E. Hahn Mechanism of Action of Antimicrobial and Antitumor Agents. Chloroquine (Resochin) 1975 Springer Berlin, Heidelberg 10.1007/978-3-642-46304-4
29. M.D. Hall, K.R. Brimacombe, M.S. Varonka, K.M. Pluchino, J.K. Monda, J. Li, M.J. Walsh, M.B. Boxer, T.H. Warren, H.M. Fales, and M.M. Gottesman Synthesis and structure-activity evaluation of isatin-β-thiosemicarbazones with improved selective activity toward multidrug-resistant cells expressing P-glycoprotein J. Med. Chem. 54 2011 5878 5889 10.1021/jm2006047
30. K. Hatano, K. Nishimura, Y. Nakai, T. Yoshida, M. Sato, A. Kawashima, M. Mukai, A. Nagahara, M. Uemura, D. Oka, M. Nakayama, H. Takayama, K. Shimizu, N. Meguro, T. Tanigawa, S. Yamaguchi, A. Tsujimura, and N. Nonomura Weekly low-dose docetaxel combined with estramustine and dexamethasone for Japanese patients with metastatic castration-resistant prostate cancer Int. J. Clin. Oncol. 18 2013 704 710 10.1007/s10147-012-0429-1
31. C. Herrmann, P.F. Salas, B.O. Patrick, C. Kock, P.J. de, Smith, M.J. Adam, and C. Orvig 1,2-Disubstituted ferrocenyl carbohydrate chloroquine conjugates as potential antimalarial agents Dalton Trans. 41 2012 6431 6442 10.1039/C2DT12247B
32. C. Hu, V. Raja Solomon, P. Cano, and H. Lee A 4-aminoquinoline derivative that markedly sensitizes tumor cell killing by Akt inhibitors with a minimum cytotoxicity to non-cancer cells Eur. J. Med. Chem. 45 2010 705 709 10.1016/j.ejmech.2009.11.017
33. C. Hu, V.R. Solomon, G. Ulibarri, and H. Lee The efficacy and selectivity of tumor cell killing by Akt inhibitors are substantially increased by chloroquine Bioorg. Med. Chem. 16 2008 7888 7893 10.1016/j.bmc.2008.07.076
34. S.R. Hubbard, and J.H. Till Protein tyrosine kinase structure and function Annu. Rev. Biochem. 69 2000 373 398 10.1146/annurev.biochem.69.1.373
35. P.B. Jensen, B.S. Sørensen, M. Sehested, P.B. Jensen, B. Sandahi, P. Grue, E.J.F. Demant, and H.H. Hansen Targeting the cytotoxicity of topoisomerase II-directed epipodophyllotoxins to tumor cells in acidic environments targeting the cytotoxicity of topoisomerase tumor cells in acidic environments Cancer Res. 1994 2959 2963
36. N. Jiang, X. Zhai, Z. Chen, C. Liang, C. Sun, J. Han, and P. Gong Design, synthesis and cytotoxicity of novel 2-arylvinyl-4-aminoquinoline derivatives Chem. Pharm. Bull. 60 2012 659 664
37. R. Kakadiya, H. Dong, A. Kumar, D. Narsinh, X. Zhang, T.-C. Chou, T.-C. Lee, A. Shah, and T.-L. Su Potent DNA-directed alkylating agents: synthesis and biological activity of phenyl N-mustard-quinoline conjugates having a urea or hydrazinecarboxamide linker Bioorg. Med. Chem. 18 2010 2285 2299 10.1016/j.bmc.2010.01.061
38. S.K. Kandi, S. Manohar, C.E. Vélez Gerena, B. Zayas, S.V. Malhotra, and D.S. Rawat C5-curcuminoid-4-aminoquinoline based molecular hybrids: design, synthesis and mechanistic investigation of anticancer activity New J. Chem. 39 2015 224 234 10.1039/C4NJ00936C
39. M.A Khan, R. Jabeen, T.H. Nasti, and O. Mohammad Enhanced anticryptococcal activity of chloroquine in phosphatidylserine-containing liposomes in a murine model J. Antimicrob. Chemother. 55 2005 223 228 doi:10.1093/jac/dkh522
40. T. Kimura, Y. Takabatake, A. Takahashi, and Y. Isaka Chloroquine in cancer therapy: a double-edged sword of autophagy Cancer Res. 73 2013 3 7 10.1158/0008-5472.CAN-12-2464
41. V.V. Kouznetsov, and A. Gómez-Barrio Recent developments in the design and synthesis of hybrid molecules based on aminoquinoline ring and their antiplasmodial evaluation Eur. J. Med. Chem. 44 2009 3091 3113 10.1016/j.ejmech.2009.02.024
42. K. Krafts, E. Hempelmann, and A. Skórska-Stania From methylene blue to chloroquine: a brief review of the development of an antimalarial therapy Parasitol. Res. 111 2012 1 6 10.1007/s00436-012-2886-x
43. Y. Li, C. de Kock, P.J. Smith, H. Guzgay, D.T. Hendricks, K. Naran, V. Mizrahi, D.F. Warner, K. Chibale, and G.S. Smith Synthesis, characterization, and pharmacological evaluation of silicon-containing aminoquinoline organometallic complexes as antiplasmodial, antitumor, and antimycobacterial agents Organometallics 32 2013 141 150 10.1021/om300945c
44. B. Loannis, J. Stephanie, G. Teresa, and E. Alessio Ruthenium anticancer compounds: challenges and expectations Chim. Int. J. Chem. 61 2007 692 697
45. M.C. Lombard, D.D. N'Da, J.C. Breytenbach, N.I. Kolesnikova, C. Tran Van Ba, S. Wein, J. Norman, P. Denti, H. Vial, and L. Wiesner Antimalarial and anticancer activities of artemisinin-quinoline hybrid-dimers and pharmacokinetic properties in mice Eur. J. Pharm. Sci. 47 2012 834 841 10.1016/j.ejps.2012.09.019
46. M.C. Lombard, D.D. N'Da, J.C. Breytenbach, P.J. Smith, and C.a. Lategan Synthesis, in vitro antimalarial and cytotoxicity of artemisinin-aminoquinoline hybrids Bioorg. Med. Chem. Lett. 21 2011 1683 1686 10.1016/j.bmcl.2011.01.103
47. M.C. Lombard, D.D. N'Da, C. Tran Van Ba, S. Wein, J. Norman, L. Wiesner, and H. Vial Potent in vivo anti-malarial activity and representative snapshot pharmacokinetic evaluation of artemisinin-quinoline hybrids Malar. J. 12 2013 71 10.1186/1475-2875-12-71
48. L. Lopez-Serra, and M. Esteller Proteins that bind methylated DNA and human cancer: reading the wrong words Br. J. Cancer 98 2008 1881 1885 10.1038/sj.bjc.6604374
49. S.J. Lunt, C. Cawthorne, M. Ali, B.a. Telfer, M. Babur, A. Smigova, P.J. Julyan, P.M. Price, I.J. Stratford, W.D. Bloomer, M.V. Papadopoulou, and K.J. Williams The hypoxia-selective cytotoxin NLCQ-1 (NSC 709257) controls metastatic disease when used as an adjuvant to radiotherapy Br. J. Cancer 103 2010 201 208 10.1038/sj.bjc.6605753
50. S. Manohar, A. Pepe, C.E. Vélez Gerena, B. Zayas, S.V. Malhotra, and D.S. Rawat Anticancer activity of 4-aminoquinoline-triazine based molecular hybrids RSC Adv. 4 2014 7062 7067 10.1039/c3ra45333b
51. I. Meinao, E. Sato, L. Andrade, M. Ferraz, and E. Atra Controlled trial with chloroquine diphosphate in systemic lupus erythematosus Lupus 5 1996 237 241 doi:10.1177/096120339600500313
52. B. Meunier Hybrid molecules with a dual mode of action: dream or reality? Acc. Chem. Res. 41 2008 69 77 10.1021/ar7000843
53. S. Morgan, P. Grootendorst, J. Lexchin, C. Cunningham, and D. Greyson The cost of drug development: a systematic review Health Policy 100 2011 4 17 10.1016/j.healthpol.2010.12.002
54. R. Morphy, C. Kay, and Z. Rankovic From magic bullets to designed multiple ligands Drug Discov. Today 9 2004 641 651 10.1016/S1359-6446(04)03163-0
55. R. Morphy, and Z. Rankovic Designed multiple ligands. An emerging drug discovery paradigm J. Med. Chem. 48 2005 6523 6543 10.1021/jm058225d
56. F.W. Muregi, and A. Ishih Next-generation antimalarial drugs: hybrid molecules as a new strategy in drug design Drug Dev. Res. 71 2010 20 32 10.1002/ddr.20345
57. M. Mushtaque, and Shahjahan Reemergence of chloroquine (CQ) analogs as multi-targeting antimalarial agents: a review Eur. J. Med. Chem. 90 2015 280 295 10.1016/j.ejmech.2014.11.022
58. D.D. N'Da, and P.J. Smith Synthesis, in vitro antiplasmodial and antiproliferative activities of a series of quinoline-ferrocene hybrids Med. Chem. Res. 23 2014 1214 1224 10.1007/s00044-013-0748-4
59. M.A Naarding, E. Baan, G. Pollakis, and W.a Paxton Effect of chloroquine on reducing HIV-1 replication in vitro and the DC-SIGN mediated transfer of virus to CD4+ T-lymphocytes Retrovirology. 4 2007 6 doi:10.1186/1742-4690-4-6
60. C. Ornelas Application of ferrocene and its derivatives in cancer research New J. Chem. 35 2011 1973 10.1039/c1nj20172g
61. P. Pakravan, S. Kashanian, M.M. Khodaei, and F.J. Harding Biochemical and pharmacological characterization of isatin and its derivatives: from structure to activity Pharmacol. Rep. 65 2013 313 335
62. M.V. Papadopoulou, and W.D. Bloomer NLCQ-1 (NSC 709257): exploiting hypoxia with a weak DNA-intercalating bioreductive drug Clin. Cancer Res. 9 2003 5714 5720
63. M.V. Papadopoulou, W.D. Bloomer, V.R. Torti, and J.G. Page Investigational new drug-directed, 5-day repeat dose toxicity study of 4-[3-(2-nitro-1-imidazolyl)-propylamino]-7-chloroquinoline hydrochloride (NLCQ-1, NSC 709257) administered with or without taxol in Sprague-Dawley rats Basic Clin. Pharmacol. Toxicol. 106 2010 497 504 10.1111/j.1742-7843.2009.00530.x
64. M.V. Papadopoulou, M. Ji, M.K. Rao, and W.D. Bloomer 4-[3-(2-Nitro-1-imidazolyl)propylamino]-7-chloroquinoline hydrochloride (NLCQ-1), a novel bioreductive compound as a hypoxia-selective cytotoxin Oncol. Res. 12 2000 185 192
65. R. Paschke, C. Paetz, T. Mueller, H.-J. Schmoll, H. Mueller, E. Sorkau, and E. Sinn Biomolecules linked to transition metal complexes-new chances for chemotherapy Curr. Med. Chem. 10 2003 2033 2044
66. B.C. Pérez, I. Fernandes, N. Mateus, C. Teixeira, and P. Gomes Recycling antimalarial leads for cancer: antiproliferative properties of N-cinnamoyl chloroquine analogues Bioorg. Med. Chem. Lett. 23 2013 6769 6772 10.1016/j.bmcl.2013.10.025
67. E. Pontiki, D. Hadjipavlou-Litina, K. Litinas, and G. Geromichalos Novel cinnamic acid derivatives as antioxidant and anticancer agents: design, synthesis and modeling studies Molecules 19 2014 9655 9674 10.3390/molecules19079655
68. S.I. Pretorius, W.J. Breytenbach, C. de Kock, P.J. Smith, and D.D. N'Da Synthesis, characterization and antimalarial activity of quinoline-pyrimidine hybrids Bioorg. Med. Chem. 21 2013 269 277 10.1016/j.bmc.2012.10.019
69. R. Raj, C. Biot, S. Carrère-Kremer, L. Kremer, Y. Guérardel, J. Gut, P.J. Rosenthal, D. Forge, and V. Kumar 7-Chloroquinoline-isatin conjugates: antimalarial, antitubercular, and cytotoxic evaluation Chem. Biol. Drug Des. 83 2014 622 629 10.1111/cbdd.12273
70. R. Raj, P. Singh, P. Singh, J. Gut, P.J. Rosenthal, and V. Kumar Azide-alkyne cycloaddition en route to 1H-1,2,3-triazole-tethered 7-chloroquinoline-isatin chimeras: synthesis and antimalarial evaluation Eur. J. Med. Chem. 62 2013 590 596 10.1016/j.ejmech.2013.01.032
71. C.S.K. Rajapakse, A. Martínez, B. Naoulou, A.A. Jarzecki, L. Suárez, C. Deregnaucourt, V. Sinou, J. Schrével, E. Musi, G. Ambrosini, G.K. Schwartz, and R.A. Sánchez-Delgado Synthesis, characterization, and in vitro antimalarial and antitumor activity of new ruthenium(II) complexes of chloroquine Inorg. Chem. 48 2009 1122 1131 10.1021/ic802220w
72. S.R. Rajski, and R.M. Williams DNA cross-linking agents as antitumor drugs Chem. Rev. 98 1998 2723 2796
73. J. Ren, J. Zhao, Y.-S. Zhou, X.-H. Liu, X. Chen, and K. Hu Synthesis and antitumor activity of novel 4-aminoquinoline derivatives Med. Chem. Res. 22 2013 2855 2861 10.1007/s00044-012-0283-8
74. A. Rilak, I. Bratsos, E. Zangrando, J. Kljun, I. Turel, Z.D. Bugarčić, and E. Alessio New water-soluble ruthenium(II) terpyridine complexes for anticancer activity: synthesis, characterization, activation kinetics, and interaction with guanine derivatives Inorg. Chem. 53 2014 6113 6126 10.1021/ic5005215
75. R. Roskoski ERBB/HER protein-tyrosine kinases: structures and small molecule inhibitors Pharmacol. Res. 87C 2014 42 59 10.1016/j.phrs.2014.06.001
76. A. Salahuddin, A. Inam, R.L. van Zyl, D.C. Heslop, C.-T. Chen, F. Avecilla, S.M. Agarwal, and A. Azam Synthesis and evaluation of 7-chloro-4-(piperazin-1-yl)quinoline-sulfonamide as hybrid antiprotozoal agents Bioorg. Med. Chem. 21 2013 3080 3089 10.1016/j.bmc.2013.03.052
77. K.V. Sashidhara, S.R. Avula, G.R. Palnati, S.V. Singh, K. Srivastava, S.K. Puri, and J.K. Saxena Synthesis and in vitro evaluation of new chloroquine-chalcone hybrids against chloroquine-resistant strain of Plasmodium falciparum Bioorg. Med. Chem. Lett. 22 2012 5455 5459 10.1016/j.bmcl.2012.07.028
78. K.V. Sashidhara, M. Kumar, R.K. Modukuri, R.K. Srivastava, A. Soni, K. Srivastava, S.V. Singh, J.K. Saxena, H.M. Gauniyal, and S.K. Puri Antiplasmodial activity of novel keto-enamine chalcone-chloroquine based hybrid pharmacophores Bioorg. Med. Chem. 20 2012 2971 2981 10.1016/j.bmc.2012.03.011
79. A. Savarino, L. Gennero, H.C. Chen, D. Serrano, F. Malavasi, J.R. Boelaert, and K. Sperber Anti-HIV effects of chloroquine: mechanisms of inhibition and spectrum of activity AIDS 15 2001 2221 2229
80. A. Savarino, J.R. Boelaert, A. Cassone, G. Majori, and R. Cauda Effects of chloroquine on viral infections: an old drug against today ' s diseases? Personal view 3 2003 722 727
81. R.H. Schirmer, H. Adler, M. Pickhardt, and E. Mandelkow Lest we forget you - methylene blue... Neurobiol. Aging 32 2011 2325.e7 2325.e16 10.1016/j.neurobiolaging.2010.12.012
82. P.H. Schlesinger, D.J. Krogstad, and B.L. Herwaldt Antimalarial agents: mechanisms of action Antimicrob. Agents Chemother. 32 1988 793 798 10.1128/AAC.32.6.793.Updated
83. R.B. Shinde, J.S. Raut, N.M. Chauhan, and S.M. Karuppayil Chloroquine sensitizes biofilms of Candida albicans to antifungal azoles Braz. J. Infect. Dis. 17 2013 395 400 doi:10.1016/j.bjid.2012.11.002
84. W.J. Slichenmyer, and D.W. Fry Anticancer therapy targeting the erbB family of receptor tyrosine kinases Semin. Oncol. 28 2001 67 79
85. V.R. Solomon, C. Hu, and H. Lee Design and synthesis of anti-breast cancer agents from 4-piperazinylquinoline: a hybrid pharmacophore approach Bioorg. Med. Chem. 18 2010 1563 1572 10.1016/j.bmc.2010.01.001
86. V.R. Solomon, and H. Lee Chloroquine and its analogs: a new promise of an old drug for effective and safe cancer therapies Eur. J. Pharmacol. 625 2009 220 233 10.1016/j.ejphar.2009.06.063
87. V.R. Solomon, and H. Lee Quinoline as a privileged scaffold in cancer drug discovery Curr. Med. Chem. 18 2011 1488 1508
88. F. Spada, A. Haemmer, D. Kuch, U. Rothbauer, L. Schermelleh, E. Kremmer, T. Carell, G. Längst, and H. Leonhardt DNMT1 but not its interaction with the replication machinery is required for maintenance of DNA methylation in human cells J. Cell Biol. 176 2007 565 571 10.1083/jcb.200610062
89. L.H. Stockwin, B. Han, S.X. Yu, M.G. Hollingshead, A. Mahmoud, W. Gul, D. Slade, A.M. Galal, and D.L. Newton Artemisinin dimer anti-cancer activity correlates with heme-catalyzed ROS generation and ER stress induction Int. J. Cancer 125 2010 1266 1275 10.1002/ijc.24496.Artemisinin
90. C.R. Chong, D.J. Sullivan jr, D.J. Sullivan Jr., and C.R. Chong New uses for old drugs Nature 448 2007 645 646
91. A.T. Taher, N.A. Khalil, E.M. Ahmed, and Y.M. Ragab Synthesis of certain 2-substituted-1H-benzimidazole derivatives as antimicrobial and cytotoxic agents Chem. Pharm. Bull. 60 2012 778 784
92. R. Thomé, S.C.P. Lopes, F.T.M. Costa, and L. Verinaud Chloroquine: modes of action of an undervalued drug Immunol. Lett. 153 2013 50 57 10.1016/j.imlet.2013.07.004
93. C. Viegas-Junior, A. Danuello, V. da Silva Bolzani, E.J. Barreiro, and C.A.M. Fraga Molecular hybridization: a useful tool in the design of new drug prototypes Curr. Med. Chem. 14 2007 1829 1852
94. S. Vlahopoulos, E. Critselis, I.F. Voutsas, S.A. Perez, M. Moschovi, C.N. Baxevanis, and G.P. Chrousos New use for old drugs? Prospective targets of chloroquines in cancer therapy Curr. Drug Targets 15 2014 843 851
95. J.J. Walsh, and A. Bell Hybrid drugs for malaria Curr. Pharm. Des. 15 2009 2970 2985
96. N.I. Wenzel, N. Chavain, Y. Wang, W. Friebolin, L. Maes, B. Pradines, M. Lanzer, V. Yardley, R. Brun, C. Herold-Mende, C. Biot, K. Tóth, and E. Davioud-Charvet Antimalarial versus cytotoxic properties of dual drugs derived from 4-aminoquinolines and mannich bases: interaction with DNA J. Med. Chem. 53 2010 3214 3226 10.1021/jm9018383
97. Y. Yan, Z. Zou, Y. Sun, X. Li, K.-F. Xu, Y. Wei, N. Jin, and C. Jiang Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model Cell Res. 23 2013 300 302 doi:10.1038/cr.2012.165
98. H. Zhang, V.R. Solomon, C. Hu, G. Ulibarri, and H. Lee Synthesis and in vitro cytotoxicity evaluation of 4-aminoquinoline derivatives Biomed. Pharmacother. 62 2008 65 69 10.1016/j.biopha.2007.04.007