Synthesis, structure-activity relationships, and biological studies of chromenochalcones as potential antileishmanial agents

Journal of Medicinal Chemistry

Volumn 57, Issue 8, 2014, Pages 3342-3357

  Gupta, Suman ^a   Shivahare, Rahul ^a   Korthikunta, Venkateswarlu ^a   Chandasana, Hardik ^a   Suthar, Manish K ^a   Agnihotri, Pragati ^a   Vishwakarma, Preeti ^a   Chaitanya, Telaprolu K ^a   Kancharla, Papireddy ^a   Khaliq, Tanvir ^a   Gupta, Shweta ^a   Bhatta, Rabi Sankar ^a   Pratap, J Venkatesh ^a   Saxena, Jitendra K ^a   Tadigoppula, Narender ^a  

^a CENTRAL DRUG RESEARCH INSTITUTE   (India)

Author keywords

[No Author keywords available]

Indexed keywords

1 [2 METHYL 2 (4 METHYL PENT 3 ENYL) 5 (2 PIPERIDIN 1 YL ETHOXY) 2H CHROMEN 6 YL] 3 [4 (2 PIPERIDIN 1 YL ETHOXY) PHENYL] PROPENONE; 1 [3 [5 HYDROXY 2 METHYL 2 (4 METHYLPENT 3 ENYL) 2H CHROMEN 6 YL] 5 (PYRIDIN 3 YL) 4,5 DIHYDRO 1H PYRAZOL 1 YL]ETHANONE; 1 [5 HYDROXY 2 METHYL 2 (4 METHYL PENT 3 ENYL) 2H CHROMEN 6YL] 3 (4 HYDROXY PHENYL) PROPENONE; 1 [5 HYDROXY 2 METHYL 2 (4 METHYLPENT 3 ENYL) 2H CHROMEN 6YL] 3 (PYRIDIN 3 YL) PROPAN 1 ONE; 1 [5 HYDROXY 2 METHYL 2 (4 METHYLPENTYL) CHROMAN 6 YL] ETHANONE; 2 HYDROXY 5 [3 [5 HYDROXY 2 METHYL 2 (4 METHYL PENT 3 ENYL) 2H CHROMEN 6 YL] 3 OXO PROPENYL] BENZALDEHYDE; ANTILEISHMANIAL AGENT; CHALCONE DERIVATIVE; CHROMENOCHALCONE 11; CHROMENOCHALCONE 16; CHROMENOCHALCONE 17; CHROMENOCHALCONE 18; CHROMENOCHALCONE 20; CHROMENOCHALCONE 21; CHROMENOCHALCONE 22; CHROMENOCHALCONE DERIVATIVE; MILTEFOSINE; SERUM ALBUMIN; STIBOGLUCONATE SODIUM; UNCLASSIFIED DRUG;

AMASTIGOTE; ANIMAL CELL; ANTIPROTOZOAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; COMPLEX FORMATION; CONTROLLED STUDY; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; DRUG PENETRATION; DRUG SYNTHESIS; HAMSTER MODEL; IC 50; IN VITRO STUDY; LEISHMANIA DONOVANI; LEISHMANIASIS; MALE; MAXIMUM PLASMA CONCENTRATION; MITOCHONDRIAL MEMBRANE POTENTIAL; NONHUMAN; PROMASTIGOTE; STRUCTURE ACTIVITY RELATION; TIME TO MAXIMUM PLASMA CONCENTRATION;

ANIMALS; ANTIPROTOZOAL AGENTS; CHALCONES; CRICETINAE; CYTOKINES; DRUG STABILITY; LEISHMANIA DONOVANI; MACROPHAGES; MEMBRANE POTENTIAL, MITOCHONDRIAL; MESOCRICETUS; NITRIC OXIDE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84899538381     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm401893j     Document Type: Article

References (57)

1. Chappuis, F.; Sundar, S.; Hailu, A.; Ghalib, H.; Alvar, J.; Boelaer, M. Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nature Rev. Microbiol. 2007, 5, 873-885
2. Murray, H. W.; Berman, J. D.; Davies, C. R. Advances in leishmaniasis Lancet 2005, 366, 1561-1577
3. Control of the Leishmaniasis: Report of a Meeting of the WHO Expert Committee on the Control of Leishmaniases; World Health Organization: Geneva, 2010.
4. Herwaldt, B. L. Leishmaniasis Lancet 1999, 354, 1191-1199
5. Olivier, M.; Gregory, D. J.; Forget, G. Subversion mechanisms by which Leishmania parasites can escape the host immune response: a signaling point of view Clin. Microbiol. Rev. 2005, 18, 293-305
6. Bogdan, C.; Gessner, A.; Solbach, W.; Rollinghoff, M. Invasion, control and persistence of Leishmania parasites Curr. Opin. Immunol. 1996, 8, 517-525
7. Assreuy, J.; Cunha, F. Q.; Epperlein, M.; Noronha-Dutra, A.; O'Donnell, C. A.; Liew, F. Y.; Moncada, S. Production of nitric oxide and superoxide by activated macrophages and killing of Leishmania major Eur. J. Immunol. 1994, 24, 672-676
8. Jha, T. K. Drug unresponsiveness and combination therapy for kala-azar Indian J. Med. Res. 2006, 123, 389-398
9. Sundar, S.; More, D. K.; Singh, M. K.; Singh, V. P.; Sharma, S.; Makharia, A. Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the indian epidemic Clin. Infect. Dis. 2000, 31, 1104-1107
10. Freitas, L. H.; Chatelin, E.; Kim, H. A. Visceral leishmaniasis treatment: What do we have, what do we need and how to deliver it? Int. J. Parasitol: Drugs Drugs Resist. 2012, 2, 11-19
11. Rybniker, J.; Goede, V.; Mertens, J.; Ortmann, M.; Kulas, W.; Kochanek, M.; Benzing, T.; Arribas, J. R.; Fätkenheuer, G. Treatment of visceral leishmaniasis with intravenous pentamidine and oral fluconazole in an HIV-positive patient with chronic renal failure-a case report and brief review of the literature Int. J. Infect. Dis. 2010, 14, 522-525
12. Mutiso, J. M.; Macharia, J. C.; Gicheru, M. M. A review of adjuvants for Leishmania vaccine candidates J. Biomed. Res. 2010, 24, 16-25
13. ávila, H. P.; Smânia, E. F. A.; Monache, F. D.; Smânia, A. Structure-activity relationship of antibacterial chalcones Bioorg. Med. Chem. 2008, 16, 9790-9794
14. Cabrera, M.; Simoens, M.; Falchi, G.; Lavaggi, M. L.; Piro, O. E.; Castellano, E. E.; Vidal, A.; Azqueta, A.; Monge, A.; de Ceráin, A. L.; Sagrera, G.; Seoane, G.; Cerecetto, H.; González, M. Synthetic chalcones, flavanones, and flavones as antitumoral agents: biological evaluation and structure-activity relationships Bioorg. Med. Chem. 2007, 15, 3356-3367
15. Chiaradia, L. D.; dos Santos, R.; Vitor, C. E.; Vieira, A. A.; Leal, P. C.; Nunes, R. J.; Calixto, J. B.; Yunes, R. A. Synthesis and pharmacological activity of chalcones derived from 2,4,6-trimethoxyacetophenone in RAW 264.7 cells stimulated by LPS: quantitative structure-activity relationships Bioorg. Med. Chem. 2008, 16, 658-667
16. Hsieh, H. K.; Lee, T. H.; Wang, J. P.; Wang, J. J.; Lin, C. N. Synthesis and anti-inflammatory effect of chalcones and related compounds Pharm. Res. 1998, 15, 39-46
17. Meng, C. Q.; Zheng, X. S.; Ni, L.; Ye, Z.; Simpson, J. E.; Worsencroft, K. J.; Hotema, M. R.; Weingarten, M. D.; Skudlarek, J. W.; Gilmore, J. M.; Hoong, L. K.; Hill, R. R.; Marino, E. M.; Suen, K. L.; Kunsch, C.; Wasserman, M. A.; Sikorski, J. A. Discovery of novel heteroaryl-substituted chalcones as inhibitors of TNF-α-induced VCAM-1 expression Bioorg. Med. Chem. Lett. 2004, 14, 1513-1517
18. Nielsen, S. F.; Boesen, T.; Larsen, M.; Schønning, K.; Kromann, H. Antibacterial chalcones-bioisosteric replacement of the 4′-hydroxy group Bioorg. Med. Chem. 2004, 12, 3047-3054
19. Uchiumi, F.; Hatano, T.; Ito, H.; Yoshida, T.; Tanuma, S. I. Transcriptional suppression of the HIV promoter by natural compounds Antiviral Res. 2003, 58, 89-98
20. Wu, J. H.; Wang, X. H.; Yi, Y. H.; Lee, K. H. Anti-AIDS agents 54. A potent anti-HIV chalcone and flavonoids from genus Desmos Bioorg. Med. Chem. Lett. 2003, 13, 1813-1815
21. Go, M. L.; Liu, M.; Wilairat, P.; Rosenthal, P. J.; Saliba, K. J.; Kirk, K. Antiplasmodial chalcones inhibit sorbitol-induced hemolysis of Plasmodium falciparum -infected erythrocytes Antimicrob. Agents Chemother. 2004, 48, 3241-3245
22. Xia, Y.; Yang, Z. Y.; Xia, P.; Bastow, K. F.; Nakanishi, Y.; Lee, K. H. Antitumor agents. Part 202: Novel 2′-amino chalcones: design, synthesis and biological evaluation Bioorg. Med. Chem. Lett. 2000, 10, 699-701
23. Bois, F.; Beney, C.; Boumendjel, A.; Mariotte, A. M.; Conseil, G.; Di Pietro, A. Halogenated chalcones with high-affinity binding to P-glycoprotein: potential modulators of multidrug resistance J. Med. Chem. 1998, 41, 4161-4164
24. Andrighetti-Fröhner, C. R.; de Oliveira, K. N.; Gaspar-Silva, D.; Pacheco, L. K.; Joussef, A. C.; Steindel, M.; Simões, C. M. O.; de Souza, A. M. T.; Magalhaes, U. O.; Afonso, I. F.; Rodrigues, C. R.; Nunes, R. J.; Castro, H. C. Synthesis, biological evaluation and SAR of sulfonamide 4-methoxychalcone derivatives with potential antileishmanial activity Eur. J. Med. Chem. 2009, 44, 755-763
25. Boeck, P.; Bandeira Falcão, C. A.; Leal, P. C.; Yunes, R. A.; Filho, V. C.; Torres-Santos, E. C.; Rossi-Bergmann, B. Synthesis of chalcone analogues with increased antileishmanial activity Bioorg. Med. Chem. 2006, 14, 1538-1545
26. Lin, Y. M.; Zhou, Y. S.; Flavin, M. T.; Zhou, L. M.; Nie, W. G.; Chen, F. C. Chalcones and flavonoids as anti-tuberculosis agents Bioorg. Med. Chem. 2002, 10, 2795-2802
27. Cheenpracha, S.; Karalai, C.; Ponglimanont, C.; Subhadhirasakul, S.; Tewtrakul, S. Anti-HIV-1 protease activity of compounds from Boesenbergia pandurata Bioorg. Med. Chem. 2006, 14, 1710-1714
28. Svetaz, L.; Tapia, A.; Lopez, S. N.; Furlan, R. L. E.; Petenatti, E.; Pioli, R.; Schmeda-Hirschmann, G.; Zacchino, S. A. Antifungal chalcones and new caffeic acid esters from Zuccagnia punctata acting against soybean infecting fungi J. Agric. Food Chem. 2004, 52, 3297-3300
29. Bolognesi, M. L.; Lizzi, F.; Perozzo, R.; Brun, R.; Cavalli, A. Synthesis of a small library of 2-phenoxy-1,4-naphthoquinone and 2-phenoxy-1,4- anthraquinone derivatives bearing anti-trypanosomal and anti-leishmanial activity Bioorg. Med. Chem. Lett. 2008, 18, 2272-2276
30. Cavalli, A.; Lizzi, F.; Bongarzone, S.; Brun, R.; Luise Krauth-Siegel, R.; Bolognesi, M. L. Privileged structure-guided synthesis of quinazoline derivatives as inhibitors of trypanothione reductase Bioorg. Med. Chem. Lett. 2009, 19, 3031-3035
31. Chen, M.; Christensen, S. B.; Blom, J.; Lemmich, E.; Nadelmann, L.; Fich, K.; Theander, T. G.; Kharazmi, A.; Licochalcone, A. a novel antiparasitic agent with potent activity against human pathogenic protozoan species of Leishmania Antimicrob. Agents Chemother. 1993, 37, 2550-2556
32. Kumar, J. K.; Narender, T.; Rao, M. S.; Rao, P. S.; Toth, G.; Balazs, B.; Duddeck, H. J. Further Dihydrochalcones from Crotolaria ramosissima J. Braz. Chem. Soc. 1999, 10, 278-280
33. Narender, T.; Shweta; Gupta, S. A convenient and biogenetic type synthesis of few naturally occurring chromeno dihydrochalcones and their in vitro antileishmanial activity Bioorg. Med. Chem. Lett. 2004, 14, 3913-3916
34. Narender, T.; Tanvir, K.; Shweta; Nishi; Goyal, N.; Gupta, S. Synthesis of chromenochalcones and evaluation of their in vitro antileishmanial activity Bioorg. Med. Chem. 2005, 13, 6543-6550
35. Bandaranayake, W. M.; Crombie, L.; Whiting, D. A. Pyridine-catalysed chromenylation of mono-chelated meta -dihydric phenols with mono-, sesqui- and di-terpene aldehydes: synthesis of rubranine and flemingins A-, B- and C-methyl ethers J. Chem. Soc., C 1971, 804-810
36. Stille, J. R.; Ward, J. A.; Leffelman, C.; Sullivan, K. A. 5-Formyl salicylaldehyde as a linker for the synthesis of benzofuran containing insulin sensitivity enhancer compounds Tetrahedron Lett. 1996, 37, 9267-9270
37. Kumar, A.; Tripathi, V. D.; Kumar, P.; Gupta, L. P.; Akanksha; Trivedi, R.; Bid, H.; Nayak, V. L.; Siddiqui, J. A.; Chakravarti, B.; Saxena, R.; Dwivedi, A.; Siddiquee, M. I.; Siddiqui, U.; Konwar, R.; Chattopadhyay, N. Design and synthesis of 1,3 biarylsulfanyl derivatives as new anti-breast cancer agents Bioorg. Med. Chem. 2011, 19, 5409-5419
38. 50 = 5.8 μM) need four steps with low overall yield.
39. 50 = 1.7 μM), however, in in vivo studies compound 17 has failed to show consistence activity on day 28. Hence, compound 14 was not taken up for in vivo studies. Compound 24 was a hydrazine derivative prepared to mask the Michael system of 16.
40. Gupta, S.; Ramesh; Sharma, S. C.; Srivastava, V. M. L. Efficacy of picroliv combination with miltefosine, an orally effective antileishmanial drug against experimental visceral leishmaniasis Acta Trop. 2005, 94, 41-47
41. Singh, G.; Jayanarayan, K. G.; Dey, C. S. Novobiocin induces apoptosis-like cell death in topoisomerase II over-expressing arsenate resistant Leishmania donovani Mol. Biochem. Parasitol. 2005, 141, 57-69
42. Verma, N. K.; Dey, C. S. Possible mechanism of miltefosine-mediated death of Leishmania donovani Antimicrob. Agents Chemother. 2004, 48, 3010-3015
43. Lakowicz, J. R. Principles of Fluorescence Spectroscopy, 3rd ed.; Springer: New York, 2006; pp 11-12.
44. Lakowicz, J. R.; Weber, G. Quenching of fluorescence by oxygen, a probe for structural fluctuations in macromolecules Biochemistry 1973, 12, 4161-4170
45. Maurice, R. E.; Camillo, A. G. Fluorescence quenching studies with proteins Anal. Biochem. 1981, 114, 199-212
46. Jayabharathi, J.; Thanikachalam, V.; Sathishkumar, R.; Jayamoorthy, K. Fluorescence investigation of the interaction of 2-(4-fluorophenyl)-1-phenyl-1 H -phenanthro[9,10- d ]imidazole with bovine serum albumin J. Photochem. Photobiol., B 2012, 117, 222-227
47. Lehrer, S. S. Solute perturbation of protein fluorescence. The quenching of the tryptophyl fluorescence of model compounds and of lysosome by iodide ion Biochemistry 1971, 10, 3254-3263
48. Gong, A.; Zhu, X.; Hu, Y.; Yu, S. A. fluorescence spectroscopic study of the interaction between epristeride and bovin serum albumine and its analytical application Talanta 2007, 73, 668-673
49. Sharma, M.; Chauhan, K.; Shivahare, R.; Vishwakarma, P.; Suthar, M. K.; Sharma, A.; Gupta, S.; Saxena, J. K.; Lal, J.; Chandra, P.; Kumar, B.; Chauhan, P. M. S. Discovery of a new class of natural product-inspired quinazolinone hybrid as potent antileishmanial agents J. Med. Chem. 2013, 56, 4374-4392
50. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays J. Immunol. Methods 1983, 65, 55-63
51. 50 in studies of drug resistance of malaria parasites Acta Trop. 1993, 55, 257-261
52. Vermes, I.; Haanen, C.; Steffens-Nakken, H.; Reutelingsperge, C. A. novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells J. Immunol. Methods 1995, 184, 39-51
53. Verma, N. K.; Singh, G.; Dey, C. S. Miltefosine induces apoptosis in arsenite-resistant Leishmania donovani promastigotes through mitochondrial dysfunction Exp. Parasitol. 2007, 116, 1-13
54. Shakya, N.; Sane, S. A.; Vishwakarma, P.; Gupta, S. Enhancement in therapeutic efficacy of miltefosine in combination with synthetic bacterial lipopeptide, Pam3Cys against experimental visceral leishmaniasis Exp. Parasitol. 2012, 131, 377-382
55. Kar, S.; Sharma, G.; Das, P. K. Fucoidan cures infection with both antimony-susceptible and -resistant strains of Leishmania donovani through Th1 response and macrophage-derived oxidants J. Antimicrob. Chemother. 2011, 66, 618-625
56. Bhattarai, S.; Tran, V. H.; Duke, C. C. Stability of [6]-gingerol and [6]-shogaol in simulated gastric and intestinal fluids J. Pharm. Biomed. Anal. 2007, 45, 648-653
57. Obach, R. S. Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: an examination of in-vitro half-life approach and nonspecific binding to microsomes Drug Metab. Dispos. 1999, 27, 1350-1359