Pharmacophore development and docking studies of the HIV-1 integrase inhibitors derived from N-methylpyrimidones, dihydroxypyrimidines, and bicyclic pyrimidinones

Chemical Biology and Drug Design

Volumn 78, Issue 1, 2011, Pages 150-160

  Telvekar, Vikas N ^a   Patel, Kavitkumar N ^a  

^a INSTITUTE OF CHEMICAL TECHNOLOGY   (India)

Author keywords

AIDS; Common pharmacophore hypothesis; Human immunodeficiency virus integrase; Integrase; Partial least square; Pharmacophore; Phase

Indexed keywords

INTEGRASE INHIBITOR; PYRIMIDINE DERIVATIVE;

ARTICLE; DRUG DESIGN; DRUG PROTEIN BINDING; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME INHIBITION; HUMAN IMMUNODEFICIENCY VIRUS 1; MOLECULAR DOCKING; PHARMACOPHORE; PRIORITY JOURNAL;

HIV INTEGRASE; HIV INTEGRASE INHIBITORS; LIGANDS; MODELS, MOLECULAR; PYRIMIDINES;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 80955179970     PISSN: 17470277     EISSN: 17470285     Source Type: Journal    
DOI: 10.1111/j.1747-0285.2011.01130.x     Document Type: Article

References (44)

1. Rang H.P., Dale M.M., Ritter J.M. (2005) Pharmacology, 3rd edn. Elsevier Inc.: Philadelphi, PA; p. 657-665.
2. Simon V., David Ho., Quarraisha A.K. (2006) HIV/AIDS epidemiology, pathogenesis, prevention, and treatment. Lancet;368:489-504.
3. + T cell homeostasis and function in advanced HIV disease. J Science;277:112-116.
4. Asante-Appiah E., Skalka A.M. (1997) Molecular mechanisms in retrovirus DNA integration. Antiviral Res;36:139-156.
5. Craigie R. (2001) HIV integrase, a brief overview from chemistry to therapeutics. J Biol Chem;276:23213-23216.
6. Zhao H., Neamati N., Mazumder A., Sunder S., Pommier Y., Burke T.R. Jr. (1997) Arylamide inhibitors of HIV-1 integrase. J Med Chem;40:1186-1194.
7. Meadows D.C., Mathews T.B., North T.W., Hadd M.J., Kuo C.L., Neamati N., Hague J.G. (2005) Synthesis and biological evaluation of geminal disulfones as HIV-1 integrase inhibitors. J Med Chem;48:4526-4534.
8. Zhao H., Neamati N., Hong H., Mazumder A., Wang S., Sunder S., Milne G.W.A., Pommier Y., Burke T.R. Jr. (1997) Coumarin-based inhibitors of HIV integrase. J Med Chem;40:242-249.
9. Neamati N., Hong H., Owen J.M., Sunder S., Winslow H.E., Christensen J.L., Zhao H., Burke T.R. Jr, Milne G.W.A., Pommier Y. (1998) Salicylhydrazine containing inhibitors of HIV-1 integrase: implication for a selective chelation in the integrase active site. J Med Chem;41:3202-3209.
10. Zhao H., Neamat N., Sunder S., Hong H., Wang S., Milne G.W.A., Pommier Y., Burke T.R. Jr. (1997) Hydrazide-containing inhibitors of HIV-1 integrase. J Med Chem;40:937-941.
11. Neamati N., Turpin J.A., Winslow H.E., Christensen J.L., Williamson K., Orr A., Rice W.G., Pommier Y., Garofalo A., Brizzi A., Campiani G.I., Nacci V. (1999) Thiazolothiazepine inhibitors of HIV-1 integrase. J Med Chem;42:3334-3341.
12. Dayam R., Sanchez T., Neamati N. (2006) Discovery and structure-activity relationship studies of a unique class of HIV-1 integrase inhibitors. Chem Med Chem;1:238-244.
13. Mazumder A., Raghavan K., Weinstein J., Kohn K.W., Pommier Y. (1995) Inhibition of human immunodeficiency virus type-1 integrase by curcumin. Biochem Pharmacol;49:1165-1170.
14. Mazumder A., Gazit A., Levitzki A., Nicklaus M., Yung J., Kohlhagen G., Pommier Y. (1995) Effects of tyrphostins, protein kinase inhibitors, on human immunodeficiency virus type 1 integrase. Biochemistry;34:15111-15122.
15. Neamati N., Mazumder A., Zhao H., Sunder S., Burke T.R. Jr, Schultz R.J., Pommier Y. (1997) Diarylsulfones, a novel class of human immunodeficiency virus type 1 integrase inhibitors. Antimicrob Agents Chemother;41:385-393.
16. Nicklaus M.C., Neamati N., Hong H., Mazumder A., Wang S., Sunder S., Chen J., Milne G.W.A., Pommier Y. (1997) HIV-1 integrase pharmacophore: discovery of inhibitors through three-dimensional database searching. J Med Chem;40:920-929.
17. Sechi M., Derudas M., Dallocchio R., Dessì A., Bacchi A., Sannia L., Carta F., Palomba M., Ragab O., Chan C., Shoemaker R., Sei S., Dayam R., Neamati N. (2004) Design and synthesis of novel indole beta-diketo acid derivatives as HIV-1 integrase inhibitors. J Med Chem;47:5298-5310.
18. Neamati N., Hong H., Mazumder A., Wang S., Sunder S., Nicklaus M.C., Milne G.W.A., Proksa B., Pommier Y. (1997) Depsides and depsidones as inhibitors of HIV-1 integrase: discovery of novel inhibitors through 3D database searching. J Med Chem;40:942-951.
19. Wai J.S., Kim B., Fisher T.E., Zhuang L., Embrey M.W., Williams P.D., Staas D.D. et al. (2007) Dihydroxypyridopyrazine-1, 6-dione HIV-1 integrase inhibitors. Bioorg Med Chem Lett;17:5595-5599.
20. Guare J.P., Wai J.S., Gomez R.P., Anthony N.J., Jolly S.M., Cortes A.R., Vacca J.P. et al. (2006) A series of 5-aminosubstituted 4-fluorobenzyl-8-hydroxy-[1, 6]naphthyridine-7-carboxamide HIV-1 integrase inhibitors. Bioorg Med Chem Lett;16:2900-2904.
21. Zhuang L., Wai J.S., Embrey M.W., Fisher T.E., Egbertson M.S., Payne L.S., Guare J.P. et al. (2003) Design and synthesis of 8-Hydroxy-[1, 6]naphthyridines as novel inhibitors of HIV-1 integrase in vitro and in infected cells. J Med Chem;46:453-456.
22. Pace P., Spieser S.A.H., Summa V. (2008) 4-Hydroxy-5-pyrrolinone-3-carboxamide HIV-1 integrase inhibitors. Bioorg Med Chem Lett;18:3865-3869.
23. Francesco M.E.D., Pace P., Fiore F., Naimo F., Bonelli F., Rowley M., Summa V. (2008) Development of 2-tbutyl-N-methyl pyrimidones as potent inhibitors of HIV integrase. Bioorg Med Chem Lett;18:2709-2713.
24. Donghi M., Kinzel O.D., Summa V. (2009) 3-Hydroxy-4-oxo-4H-pyrido[1, 2-a]pyrimidine-2-carboxylates - a new class of HIV-1 integrase inhibitors. Bioorg Med Chem Lett;19:1930-1934.
25. Pace P., Francesco M.E.D., Gardelli C., Harper S., Muraglia E., Nizi E., Orvieto F. et al. (2007) Dihydroxypyrimidine-4-carboxamides as novel potent and selective HIV integrase inhibitors. J Med Chem;50:2225-2239.
26. Gardelli C., Nizi E., Muraglia E., Crescenzi B., Ferrara M., Orvieto F., Pace P. et al. (2007) Discovery and synthesis of hiv integrase inhibitors: development of potent and orally bioavailable N-methyl pyrimidones. J Med Chem;50:4953-4975.
27. Muraglia E., Kinzel O., Gardelli C., Crescenzi B., Donghi M., Ferrara M., Nizi E. et al. (2008) Design and synthesis of bicyclic pyrimidinones as potent and orally bioavailable HIV-1 integrase inhibitors. J Med Chem;51:861-874.
28. Summa V., Petrocchi A., Bonelli F., Crescenzi B., Donghi M., Ferrara M., Fiore F. et al. (2008) Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection. J Med Chem;51:5843-5855.
29. Xu Y.W., Zhao G.S., Shin C.G., Zang H.C., Lee C.K., Lee Y.S. (2003) Caffeoyl naphtalenesulfonamide derivatives as HIV integrase inhibitors. Bioorg Med Chem;11:3589.
30. Mustata G.I., Brigo A., Briggs J.M. (2004) HIV-1 integrase pharmacophore model derived from diverse classes of inhibitors. Bioorg Med Chem Lett;14:1447-1454.
31. Carlson H.A., Masukawa K.M., Rubins K., Bushman F.D., Jorgensen W.L., Lins R.D., Briggs J.M., McCammon J.A. (2003) Developing a dynamic pharmacophore model for HIV-1 integrase. J Med Chem;43:2100-2114.
32. Deng J., Lee K.W., Sanchez T., Cui M., Neamati N., Briggs J.M. (2005) Dynamic receptor-based pharmacophore model development and its application in designing novel HIV-1 integrase inhibitors. J Med Chem;48:1496-1505.
33. Makhija M.T., Kulkarni V.M. (2001) Molecular electrostatic potentials as input for the alignment of HIV-1 integrase inhibitors in 3D QSAR. J Comput Aided Mol Des;15:961-978.
34. Saiz-Urra L., Gonzalez M.P., Gomez G. (2007) Quantitative structure-activity relationship studies of HIV-1 integrase inhibition. 1. GETAWAY descriptors. Eur J Med Chem;42:64-70.
35. Nunthaboot N., Tonmunphean S., Parasuk V., Wolschannb P., Kokpol S. (2006) Three dimensional quantitative structure: activity relationship studies on diverse structural classes of HIV-1 integrase inhibitors using CoMFA and CoMSIA. Eur J Med Chem;41:1359-1372.
36. Savarino A. (2007) In-Silico docking of HIV-1 integrase inhibitors reveals a novel drug type acting on an enzyme/DNA reaction intermediate. Retrovirology;4:21.
37. Marriott D.P., Dougall I.G., Meghani P., Liu Y.J., Flower D.R. (1999) Lead generation using pharmacophore mapping and three-dimensional database searching: application to muscarinic M3 receptor antagonists. J Med Chem;42:3210-3216.
38. Palomer A., Cabre F., Pascual J., Campos J., Trujillo M.A., Entrena A., Gallo M.A., Garcia L., Mauleon D., Espinosa A. (2002) Identification of novel cyclooxygenase-2 selective inhibitors using pharmacophore models. J Med Chem;47:1402-1411.
39. Kaminski J.J., Rane D.F., Snow M.E., Weber L., Rothofsky M.L., Anderson S.D., Lin S.L. (1997) Identification of novel farnesyl protein transferase inhibitors using three-dimensional database searching methods. J Med Chem;40:4103-4112.
40. Telvekar V.N., Kundaikar H.S., Patel K.N., Chaudhari H.K. (2008) 3D-QSAR and molecular docking studies on aryl benzofuran-2-yl ketoxime derivatives as Candida albicans N-Myristoyltransferase inhibitors. QSAR Combi Sci;27:1193-1203.
41. Banks J.L., Beard H.S., Cao Y., Cho A.E., Damm W., Farid R., Felts A.K. et al. (2005) Integrated modeling program, applied chemical theory (IMPACT). J Comput Chem;26:1752-1780.
42. Billich A. (2003) S-1360 (Shionogi-GlaxoSmithKline). Curr Opin Investig Drugs;4:206-209.
43. Grinsztejn B., Nguyen B.Y., Katlama C., Gatell J.M., Lazzarin A., Vittecoq D., Gonzalez C.J., Chen J., Harvey C.M., Isaacs R.D. (2007) Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet;369:1261-1269.
44. Dejesus E., Berger D., Markowitz M., Cohen C., Hawkins T., Ruane P., Elion R., Farthing C., Zhong L., Cheng A.K., McColl D., Kearney B.P. (2006) Antiviral activity, pharmacokinetics, and dose response of the HIV-1 integrase inhibitor GS-9137 (JTK-303) in treatment-naive and treatment-experienced patients. J Acquir Immune Defic Syndr;43:1-5.