2-Amido-3-(1H-Indol-3-yl)-N-substitued-propanamides as a new class of falcipain-2 inhibitors. 1. Design, synthesis, biological evaluation and binding model studies

Molecules

Volumn 14, Issue 1, 2009, Pages 494-508

  Zhu, Jin ^a   Chen, Tong ^a   Chen, Lili ^b   Lu, Weiqiang ^a   Che, Peng ^a   Huang, Jin ^a   Li, Honglin ^a   Li, Jian ^a   Jiang, Hualiang ^a,b  

^a EAST CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^b SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

Author keywords

3 (1H indol 3 yl) propanamide derivatives; Falcipain 2 inhibitor; Malaria; SAR

Indexed keywords

AMIDE; CYSTEINE PROTEINASE; CYSTEINE PROTEINASE INHIBITOR; FALCIPAIN 2;

ANIMAL; ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; COMPUTER SIMULATION; DRUG DESIGN; HUMAN; MALARIA FALCIPARUM; METABOLISM; PLASMODIUM FALCIPARUM; PROTEIN CONFORMATION; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

AMIDES; ANIMALS; COMPUTER SIMULATION; CYSTEINE ENDOPEPTIDASES; CYSTEINE PROTEINASE INHIBITORS; DRUG DESIGN; HUMANS; MALARIA, FALCIPARUM; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PLASMODIUM FALCIPARUM; PROTEIN CONFORMATION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 59349095066     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules14010494     Document Type: Article

References (31)

1. Vangapandu, S.; Jain, M.; Kaur, K.; Patil, P.; Patel, S.R.; Jain, R. Recent advances in antimalarial drug development. Med. Res. Rev. 2007, 27, 65-107.
2. Fidock, D.A.; Rosenthal, P.J.; Croft, S.L.; Brun, R.; Nwaka, S. Antimalarial drug discovery: Efficacy models for compound screening. Nat. Rev. Drug Discov. 2004, 3, 509-520.
3. Wellems, T.E.; Plowe, C.V. Chloroquine-resistant malaria. J. Infect. Dis. 2001, 184, 770-776.
4. Trape, J.F. The public health impact of chloroquine resistance in Africa. Am. J. Trop. Med. Hyg. 2001, 64, 12-17.
5. Plowe, C.V. Monitoring antimalarial drug resistance: making the most of the tools at hand. J. Exp. Biol. 2003, 206, 3745-3752.
6. Shenai, B.R.; Sijwali, P.S.; Singh, A.; Rosenthal, P.J. Characterization of native and recombinant falcipain-2, a principal trophozoite cysteine protease and essential hemoglobinase of Plasmodium falciparum. J. Biol. Chem. 2000, 275, 29000-29010.
7. Dua, M.; Raphael, P.; Sijwali, P.S.; Rosenthal, P.J.; Hanspal, M. Recombinant falcipain-2 cleaves erythrocyte membrane ankyrin and protein 4.1. Mol. Biochem. Parasitol. 2001, 116, 95-99.
8. Rosenthal, P.J.; Olson, J.E.; Lee, G.K.; Palmer, J.T.; Klaus, J.L.; Rasnick, D. Antimalarial effects of vinyl sulfone cysteine proteinase inhibitors. Antimicrob. Agents Chemother. 1996, 40, 1600-1603.
9. Shenai, B.R; Lee, B.J.; Alvarez-Hernandez, A.; Chong, P.Y.; Emal, C.D.; Neitz, R.J.; Roush, W.R.; Rosenthal, P.J. Structure-activity relationships for inhibition of cysteine protease activity and development of Plasmodium falciparum by peptidyl vinyl sulfones. Antimicrob. Agents Chemother. 2003, 47, 154-160.
10. Lee, B.J.; Singh, A.; Chiang, P.; Kemp, S.J.; Goldman, E.A.; Weinhouse, M.I.; Vlasuk, G.P.; Rosenthal, P.J. Antimalarial activities of novel synthetic cysteine protease inhibitors. Antimicrob. Agents Chemother. 2003, 47, 3810-3814.
11. Domínguez, J.N.; López, S.; Charris, J.; Iarruso, L.; Lobo, G.; Semenov, A.; Olson, J.E.; Rosenthal, P.J. Synthesis and antimalarial effects of phenothiazine inhibitors of a Plasmodium falciparum cysteine protease. J. Med. Chem. 1997, 40, 2726-2732.
12. Huang, L.; Lee, A.; Ellman, J.A. Identification of potent and selective mechanism-based inhibitors of the cysteine protease cruzain using solid-phase parallel synthesis. J. Med. Chem. 2002, 45, 676-684.
13. Greenbaum, D.C.; Mackey, Z.; Hansell, E.; Doyle, P.; Gut, J.; Caffrey, C.R.; Lehrman, J.; Rosenthal, P.J.; McKerrow, J.H.; Chibale, K. Synthesis and structure-activity relationships of parasiticidal thiosemicarbazone cysteine protease inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruzi. J. Med. Chem. 2004, 47, 3212-3219.
14. Desai, P.V.; Patny, A.; Sabnis, Y.; Tekwani, B.; Gut, J.; Rosenthal, P.; Srivastava, A.; Avery, M. Identification of novel parasitic cysteine protease inhibitors using virtual screening. 1. The ChemBridge database. J. Med. Chem. 2004, 47, 6609-6615.
15. Domínguez, J.N.; León, C.; Rodrigues, J.; Gamboa de Domínguez, N.; Gut, J.; Rosenthal, P.J. Synthesis and evaluation of new antimalarial phenylurenyl chalcone derivatives. J. Med. Chem. 2005, 48, 3654-3658.
16. Desai, P.V.; Patny, A.; Gut, J.; Rosenthal, P.J.; Tekwani, B.; Srivastava, A.; Avery, M. Identification of novel parasitic cysteine protease inhibitors by use of virtual screening. 2. The available chemical directory. J. Med. Chem. 2006, 49, 1576-1584.
17. Batra, S.; Sabnis, Y.A.; Rosenthal, P.J.; Avery, M.A. Structure-based approach to falcipain-2 inhibitors: Synthesis and biological evaluation of 1,6,7-trisubstituted dihydroisoquinolines and isoquinolines. Bioorg. Med. Chem. 2003, 11, 2293-2299.
18. Chiyanzu, I.; Hansell, E.; Gut, J.; Rosenthal, P.J.; Mckerrow, J.H.; Chibale, K. Synthesis and evaluation of isatins and thiosemicarbazone derivatives against cruzain, falcipain-2 and rhodesain. Bioorg. Med. Chem. Lett. 2003, 13, 3527-3530.
19. Chipeleme, A.; Gut, J.; Rosenthal, P.J.; Chibale, K. Synthesis and biological evaluation of phenolic Mannich bases of benzaldehyde and (thio)semicarbazone derivatives against the cysteine protease falcipain-2 and a chloroquine resistant strain of Plasmodium falciparum. Bioorg. Med. Chem. 2007, 15, 273-282.
20. Rosenthal, P.J.; Wollish, W.S.; Palmer, J.T.; Rasnick, D. Antimalarial effects of peptide inhibitors of a Plasmodium falciparum cysteine proteinase. J. Clin. Invest. 1991, 88, 1467-1472.
21. Rosenthal, P.J.; Lee, G.K.; Smith, R.E. Inhibition of a Plasmodium vinckei cysteine proteinase cures murine malaria. J. Clin. Invest. 1993, 91, 1052-1056.
22. Sajid, M.; McKerrow, J. Cysteine proteases of parasitic organisms. Mol. Biochem. Parasitol. 2002, 120, 1-21.
23. Jorgensen, W.L. The many roles of computation in drug discovery. Science 2004, 303, 1813-1818.
24. Sabnis, Y.; Rosenthal, P.J.; Desai, P.; Avery, M.A. Homology modeling of falcipain-2: Validation, de novo ligand design and synthesis of novel inhibitors. J. Biomol. Struct. Dyn. 2002, 19, 765-774.
25. Goh, L.L.; Sim, T.S. Homology modeling and mutagenesis analyses of Plasmodium falciparum falcipain 2A: Implications for rational drug design. Biochem. Biophys. Res. Commun. 2004, 323, 565-572.
26. Hogg, T.; Nagarajan, K.; Herzberg, S.; Chen, L.; Shen, X.; Jiang, H.; Wecke, M.; Blohmke, C.; Hilgenfeld, R.; Schmidt, C.L. Structural and functional characterization of Falcipain-2, a hemoglobinase from the malarial parasite Plasmodium falciparum. J. Biol. Chem. 2006, 281, 25425-25437.
27. Wang, S.X.; Pandey, K.C.; Somoza, J.R.; Sijwali, P.S.; Kortemme, T.; Brinen, L.S.; Fletterick, R.J.; Rosenthal, P.J.; Mckerrow, J.H. Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial protease. Proc. Natl. Acad. Sci. USA 2006, 103, 11503-11508.
28. Li, H.; Chen, L.; Huang, J.; Zhu, J.; Shen, X.; Li, J.; Hilgenfeld, R.; Jiang, H. Identification of novel Falcipain-2 inhibitors as potential antimalarial agents through structure-based virtual screening. Submitted to J. Med. Chem.
29. Peters, W. Drug resistance in Plasmodium berghei Vincke and Lips, 1948. I. Chloroquine resistance. Expl. Parasite 1965, 17, 80-89.
30. Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The Protein Data Bank. Nucleic Acids Res. 2000, 28, 235-242.
31. Rosenthal, P.J.; McKerrow, J.H.; Rasnick, D.; Leech, J.H. Plasmodium falciparum: Inhibitors of lysosomal cysteine proteinases inhibit a trophozoite proteinase and block parasite development. Mol. Biochem. Parasitol. 1989, 35, 177-183.