Computer-aided design, synthesis, and biological activity evaluation of potent fusion inhibitors targeting HIV-1 gp41

Medicinal Chemistry

Volumn 7, Issue 4, 2011, Pages 309-316

  Tan, Jun Jian ^a   Zhang, Bin ^a   Cong, Xiao Jing ^a   Yang, Lei Fu ^a   Liu, Bin ^a   Kong, Ren ^a   Kui, Zhi Yao ^a   Wang, Cun Xin ^a   Hu, Li Ming ^a  

^a BEIJING UNIVERSITY OF TECHNOLOGY   (China)

Author keywords

Drug design; Fusion inhibitors; gp41; HIV; Optimization

Indexed keywords

2 HYDROXY 4 [3 (METHOXYCARBONYL) 2 METHYL 5 PHENYL 1H PYRROL 1 YL]BENZOIC ACID; 4 (3 ACETYL 2 METHYL 5 PHENYL 1H PYRROL 1 YL) 2 HYDROXYBENZOIC ACID; 4 (3 ACETYL 2,5 DIMETHYL 1H PYRROL 1 YL) 2 HYDROXYBENZOIC ACID; 4 (3 BENZOYL 2 METHYL 5 PHENYL 1H PYRROL 1 YL) 2 HYDROXYBENZOIC ACID; 4 (3 BENZOYL 2,5 DIMETHYL 1H PYRROL 1 YL) 2 HYDROXYBENZOIC ACID; 4 [3 BENZOYL 2 METHYL 5 (4 NITROPHENYL) 1H PYRROL 1 YL] 2 HYDROXYBENZOIC ACID; C 34; ENFUVIRTIDE; GLYCOPROTEIN GP 41; HUMAN IMMUNODEFICIENCY VIRUS FUSION INHIBITOR; LPF 1; LPF 10; LPF 100; LPF 101; LPF 102; LPF 103; LPF 105; LPF 107; LPF 108; LPF 11; LPF 111; LPF 113; LPF 115; LPF 12; LPF 123; LPF 124; LPF 125; LPF 126; LPF 128; LPF 13; LPF 132; LPF 135; LPF 14; LPF 15; LPF 155; LPF 158; LPF 16; LPF 166; LPF 17; LPF 18; LPF 181; LPF 188; LPF 19; LPF 2; LPF 20; LPF 21; LPF 22; LPF 23; LPF 24; LPF 25; LPF 26; LPF 27; LPF 28; LPF 282; LPF 3; LPF 30; LPF 31; LPF 32; LPF 33; LPF 36; LPF 37; LPF 38; LPF 39; LPF 40; LPF 41; LPF 42; LPF 44; LPF 45; LPF 46; LPF 463; LPF 47; LPF 48; LPF 49; LPF 5; LPF 50; LPF 52; LPF 53; LPF 54; LPF 55; LPF 56; LPF 57; LPF 6; LPF 60; LPF 61; LPF 62; LPF 63; LPF 64; LPF 65; LPF 66; LPF 67; LPF 68; LPF 69; LPF 7; LPF 70; LPF 71; LPF 72; LPF 729; LPF 73; LPF 74; LPF 75; LPF 76; LPF 77; LPF 78; LPF 79; LPF 8; LPF 81; LPF 85; LPF 87; LPF 88; LPF 89; LPF 93; LPF 94; LPF 98; SIFUVIRTIDE; T 21; TIFUVIRTIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; COMPUTER AIDED DESIGN; CONFORMATIONAL TRANSITION; DRUG DESIGN; DRUG POTENCY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; HUMAN IMMUNODEFICIENCY VIRUS 1; IC 50; IN VITRO STUDY; MOLECULAR DOCKING; NONHUMAN; PRIORITY JOURNAL;

ANTI-HIV AGENTS; BENZOIC ACIDS; COMPUTER-AIDED DESIGN; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; HIV ENVELOPE PROTEIN GP41; HIV FUSION INHIBITORS; HIV INFECTIONS; HIV-1; HUMANS; INHIBITORY CONCENTRATION 50; MOLECULAR STRUCTURE; MOLECULAR TARGETED THERAPY; PYRROLES;

EID: 79959340169     PISSN: 15734064     EISSN: 18756638     Source Type: Journal    
DOI: 10.2174/157340611796150905     Document Type: Article

References (23)

1. Tan, J. J.; Cong, X. J.; Hu, L. M.; Wang, C. X.; Jia, L.; Liang, X. J. Therapeutic strategies underpinning the development of novel techniques for the treatment of HIV infection. Drug Discov. Today, 2010, 15 (5-6), 186-197.
2. Chan, D. C.; Fass, D.; Berger, J. M.; Kim, P. S. Core structure of gp41 from the HIV envelope glycoprotein. Cell, 1997, 89 (2), 263-273. (Pubitemid 27199898)
3. Chan, D. C.; Chutkowski, C. T.; Kim, P. S. Evidence that a prominent cavity in the coiled coil of HIV type 1 gp41 is an attractive drug target. Proc. Natl. Acad. Sci. USA, 1998, 95 (26), 15613-15617. (Pubitemid 29018748)
4. Naider, F.; Anglister, J. Peptides in the treatment of AIDS. Curr. Opin. Struct. Biol., 2009, 19 (4), 473-482.
5. Debnath, A. K.; Radigan, L.; Jiang, S. B. Structure-based identification of small molecule antiviral compounds targeted to the gp41 core structure of the human immunodeficiency virus type 1. J. Med. Chem., 1999, 42 (17), 3203-3209. (Pubitemid 29409709)
6. Frey, G.; Rits-Volloch, S.; Zhang, X. Q.; Schooley, R. T.; Chen, B.; Harrison, S. C. Small molecules that bind the inner core of gp41 and inhibit HIV envelope-mediated fusion. Proc. Natl. Acad. Sci. U. S. A., 2006, 103 (38), 13938-13943. (Pubitemid 44452961)
7. Jiang, S. B.; Lu, H.; Liu, S. W.; Zhao, Q.; He, Y. X.; Debnath, A. K. N-substituted pyrrole derivatives as novel human immunodeficiency virus type 1 entry inhibitors that interfere with the gp41 six-helix bundle formation and block virus fusion. Antimicrob. Agents Chemother., 2004, 48 (11), 4349-4359. (Pubitemid 39434898)
8. Lalezari, J. P.; Eron, J. J.; Carlson, M.; Cohen, C.; DeJesus, E.; Arduino, R. C.; Gallant, J. E.; Volberding, P.; Murphy, R. L.; Valentine, F.; Nelson, E. L.; Sista, P. R.; Dusek, A.; Kilby, J. M. A phase II clinical study of the long-term safety and antiviral activity of enfuvirtide-based antiretroviral therapy. AIDS, 2003, 17 (5), 691-698. (Pubitemid 36521075)
9. Tan, J. J.; Chen, W. Z.; Wang, C. X. Investigating interactions between HIV-1 gp41 and inhibitors by molecular dynamics simulation and MM-PBSA/GBSA calculations. J. Mol. Struct. Theochem, 2006, 766 (2-3), 77-82.
10. Tan, J. J.; Kong, R.; Wang, C. X.; Chen, W. Z. Gp41 hydrophobic pocket entry inhibitor linear interaction energy MD simulation. J. Mol. Struct. Theochem, 2004, 682 (1-3), 9-15.
11. Tan, J. J.; Kong, R.; Chen, W. Z.; Wang, C. X. Studies on binding free energies and the binding mode by docking and MM-PBSA in gp41-ligand complex. Mol. Simul., 2005, 31 (14-15), 1051-1056. (Pubitemid 43065404)
12. Wang, Y.; Lu, H.; Zhu, Q.; Jiang, S. B.; Liao, Y. Structure-based design, synthesis and biological evaluation of new Ncarboxyphenylpyrrole derivatives as HIV fusion inhibitors targeting gp41. Bioorg. Med. Chem. Lett., 2010, 20 (1), 189-192.
13. Liu, B.; Joseph, R. W.; Dorsey, B. D.; Schiksnis, R. A.; Northrop, K.; Bukhtiyarova, M.; Springman, E. B. Structure-based design of substituted biphenyl ethylene ethers as ligands binding in the hydrophobic pocket of gp41 and blocking the helical bundle formation. Bioorg. Med. Chem. Lett., 2009, 19 (19), 5693-5697.
14. Wang, C. X.; Cong, X. J.; Kong, R.; Tan, J. J.; Chen, W. Z. Binding mode of HIV-1 gp41 with its inhibitor NB-2. Journal of Beijing University of Technology, 2010, 36 (8), 1118-1123.
15. Cong, X. J.; Tan, J. J.; Liu, M.; Chen, W. Z.; Wang, C. X. Computational Study of Binding Mode for N-substituted Pyrrole Derivatives to HIV-1 gp41. Prog. Biochem. Biophys., 2010, 37 (8), 904-915.
16. Payne, A. W.; Glen, R. C. Molecular recognition using a binary genetic search algorithm. J. Mol. Graph., 1993, 11, 74-91.
17. Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. K.; Olson, A. J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem., 1998, 19 (14), 1639-1662. (Pubitemid 128590223)
18. Sheridan, R. P.; Nachbar, R. B.; Bush, B. L. Extending the Trend Vector - the Trend Matrix and Sample-Based Partial Least-Squares. J. Comput.-Aided Mol. Des., 1994, 8 (3), 323-340.
19. Murtagh, F. A Survey of Recent Advances in Hierarchical- Clustering Algorithms. Comput. J., 1983, 26 (4), 354-359. (Pubitemid 14590891)
20. Wallace, A. C.; Laskowski, R. A.; Thornton, J. M. Ligplot - a Program to Generate Schematic Diagrams of Protein Ligand Interactions. Protein Eng., 1995, 8 (2), 127-134.
21. SYBYL, 7.3; Tripos Inc.: St. Louis.
22. Wang, C. X.; Liu, B.; He, H. Q.; Zhang, X. Y.; Tan, J. J.; Chen, W. Z. Novel in vitro screening systems for HIV-1 fusion inhibitors. CN 101498722A, 2009.
23. McCammon, J. A. Target flexibility in molecular recognition. Bba- Proteins Proteom., 2005, 1754 (1-2), 221-224. (Pubitemid 41797701)