Small-molecular HIV-1 integrase inhibitors: The 2001-2002 update

Current Pharmaceutical Design

Volumn 9, Issue 22, 2003, Pages 1789-1802

  Dayam, Raveendra ^a   Neamati, Nouri ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

5 CITEP; Drug discovery; HIV 1 integrase; Inhibitors; S 1360; Structure based drug design

Indexed keywords

1 [5 (4 FLUOROBENZYL) 2 FURYL] 3 (1,2,4 TRIAZOL 3 YL) 1,3 PROPANEDIONE; ANTIVIRUS AGENT; AROMATIC COMPOUND; CATECHOL DERIVATIVE; CICHORIC ACID; COMPLESTATIN; DNA; FLAVONOID; INTEGRACIN A; INTEGRACIN B; INTEGRACIN C; INTEGRAMIDE; INTEGRAMYCIN; INTEGRASE; INTEGRASE INHIBITOR; INTEGRASTATIN A; INTEGRASTATIN B; LAMELLARIN DERIVATIVE; LAMELLARIN H; LAUROLISTINE; LITHOSPERMIC ACID; NATURAL PRODUCT; OXOACID; PROTEINASE INHIBITOR; QUINOLINE DERIVED ANTIINFECTIVE AGENT; RNA DIRECTED DNA POLYMERASE INHIBITOR; SESQUITERPENE DERIVATIVE; TANNIN DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VIRUS DNA;

ANTIVIRAL ACTIVITY; CATALYSIS; CLINICAL TRIAL; COMPUTER AIDED DESIGN; DRUG DESIGN; DRUG MECHANISM; DRUG POTENTIATION; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TARGETING; HOST CELL; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IC 50; LIFE CYCLE; PRIORITY JOURNAL; PROVIRUS; REVIEW; VIRUS MUTATION; VIRUS RECOMBINANT; VIRUS REPLICATION; CHEMICAL STRUCTURE; CHEMISTRY; STRUCTURE ACTIVITY RELATION;

DRUG DESIGN; HIV INTEGRASE INHIBITORS; HUMANS; MOLECULAR STRUCTURE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0041488800     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/1381612033454469     Document Type: Review

References (56)

1. Hazuda DJ, Hastings JC, Wolfe AL, Emini EA. A novel assay for the DNA strand-transfer reaction of HIV-1 integrase. Nucleic Acids Res 1994; 22: 1121-2.
2. Mazumder A, Neamati N, Sunder S, Owen J, Pommier Y. In Methods in Cellular and Molecular Biology: Antiviral Evaluation, D Kinchington; R Schinazi, eds.; The Humana Press, Inc.: Totowa, NJ, 1999, pp. 327-38.
3. Chow SA. In vitro assays for activities of retroviral integrase. Methods 1997; 12: 306-17.
4. Debyser Z, Cherepanov P, Pluymers W, De Clercq E. Assays for the evaluation of HIV-1 integrase inhibitors. Methods Mol Biol 2001; 160: 139-55.
5. Neamati N. Patented small molecule inhibitors of HIV-1 integrase: a ten-year saga. Expert Opin Ther Pat 2002; 12: 709-24.
6. Neamati N, Sunder S, Pommier Y. Design and discovery of HIV-1 integrase inhibitors. Drug Discovery Today 1997; 2: 487-98.
7. Neamati N, Marchand C, Pommier Y. HIV-1 integrase inhibitors: past, present, and future. Adv Pharmacol 2000; 49: 147-65.
8. Pommier Y, Marchand C, Neamati N. Retroviral integrase inhibitors year 2000: update and perspectives [In Process Citation]. Antiviral Res 2000; 47: 139-48.
9. Este JA, Cabrera C, Schols D, Cherepanov P, Gutierrez A, Witvrouw M, et al. Human immunodeficiency virus glycoprotein gp120 as the primary target for the antiviral action of AR177 (Zintevir). Mol Pharmacol 1998; 53: 340-5.
10. Pluymers W, Neamati N, Pannecouque C, Fikkert V, Marchand C, Burke TR, Jr., et al. Viral entry as the primary target for the anti-HIV activity of chicoric acid and its tetra-acetyl esters. Mol Pharmacol 2000; 58: 641-8.
11. Yoshinaga T, Sato A, Fujishita T, Fujiwara T. In 9th Conference on retroviruses and opportunistic infections: Seattle. 2002.
12. Neamati N, Barchi Jr. JJ. New paradigms in drug design and discovery. Curr Top Med Chem 2002; 2: 211-27.
13. Singh SB, Zink DL, Bills GF, Pelaez F, Teran A, Collado J, et al. Discovery, structure and HIV-1 integrase inhibitory activities of integracins, novel dimeric alkyl aromatics from Cytonaema sp. Tetrahedron Lett. 2002; 43: 1617-20.
14. Singh SB, Zink DL, Quamina DS, Pelaez F, Teran A, Felock P, et al. Integrastatins: structure and HIV-1 integrase inhibitory activities of two novel racemic tetracyclic aromatic heterocycles produced by two fungal species. Tetrahedron Lett 2002; 43: 2351-4.
15. Singh SB, Zink DL, Heimbach B, Genilloud O, Teran A, Silverman KC, et al. Structure, stereochemistry, and biological activity of integramycin, a novel hexacyclic natural product produced by Actinoplanes sp. that inhibits HIV-1 integrase. Org Lett 2002; 4: 1123-6.
16. Zhang CF, Nakamura N, Tewtrakul S, Hattori M, Sun QS, Wang ZT, et al. Sesquiterpenes and alkaloids from Lindera chunii and their inhibitory activities against HIV-1 integrase. Chem Pharm Bull 2002; 50: 1195-200.
17. Tewtrakul S, Nakamura N, Hattori M, Fujiwara T, Supavita T. Flavanone and flavonol glycosides from the leaves of Thevetia peruviana and their HIV-1 reverse transcriptase and HIV-1 integrase inhibitory activities. Chem Pharm Bull 2002; 50: 630-5.
18. Ahn MJ, Kim CY, Lee JS, Kim TG, Kim SH, Lee CK, et al. Inhibition of HIV-1 integrase by galloyl glucoses from Terminalia chebula and flavonol glycoside gallates from Euphorbia pekinensis. Planta Med 2002; 68: 457-9.
19. Abd-Elazem IS, Chen HS, Bates RB, Huang RCC. Isolation of two highly potent and non-toxic inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase from Salvia miltiorrhiza. Antiviral Res 2002; 55: 91-106.
20. Reinke RA, King PJ, Victoria JG, McDougall BR, Ma G, Mao Y, et al. Dicaffeoyltartaric acid analogues inhibit human immunodeficiency virus type 1 (HIV-1) integrase and HIV-1 replication at nontoxic concentrations. J Med Chem 2002: 45: 3669-83.
21. Ridley CP, Reddy MV, Rocha G, Bushman ED, Faulkner DJ. Total synthesis and evaluation of lamellarin alpha 20-Sulfate analogues. Bioorg Med Chem 2002; 10: 3285-90.
22. Stanwell C, Ye B, Yuspa SH, Burke TR, Jr. Cell protein cross-linking by erbstatin and related compounds. Biochem Pharmacol 1996; 52: 475-80.
23. Mazumder A, Gazit A, Levitzki A, Nicklaus M, Yung J, Kohlhagen G, et al. Effects of tyrphostins, protein kinase inhibitors, on human immunodeficiency virus type 1 integrase. Biochemistry 1995; 34: 15111-22.
24. Dupont R, Jeanson L, Mouscadet JF, Cotelle P. Synthesis and HIV-1 integrase inhibitory activities of catechol and bis- catechol derivatives. Bioorg Med Chem Lett 2001; 11: 3175-8.
25. Neamati N, Hong H, Sunder S, Milne GW, Pommier Y. Potent inhibitors of human immunodeficiency virus type 1 integrase: identification of a novel four-point pharmacophore and tetracyclines as novel inhibitors. Mol Pharmacol 1997; 52: 1041-55.
26. Zouhiri F, Desmaele D, d'Angelo J, Ourevitch M, Mouscadet JF, Leh H, et al. HIV-1 replication inhibitors of the styrylquinoline class: incorporation of a masked diketo acid pharmacophore. Tetrahedron Lett 2001; 42: 8189-92.
27. Singh SB, Jayasuriya H, Salituro GM, Zink DL, Shafiee A, Heimbuch B, et al. The complestatins as HIV-1 integrase inhibitors. Efficient isolation, structure elucidation, and inhibitory activities of isocomplestatin, chloropeptin 1, new complestatins, A and B, and acid-hydrolysis products of chloropeptin I. J Nat Prod 2001; 64: 874-82.
28. Singh SB, Herath K, Guan ZQ, Zink DL, Dombrowski AW, Polishook JD, et al. Integramides A and B, two novel nonribosomal linear peptides containing nine C-alpha-methyl amino acids produced by fungal fermentations that are inhibitors of HIV-1 integrase. Organic Lett 2002; 4: 1431-4.
29. Lubkowski J, Yang F, Alexandratos J, Wlodawer A, Zhao H, Burke TR, Jr., et al. Structure of the catalytic domain of avian sarcoma virus integrase with a bound HIV-1 integrase-targeted inhibitor. Proc Natl Acad Sci U S A 1998; 95: 4831-6.
30. Rowley DC, Hansen MST, Rhodes D, Sotriffer CA, Ni HH, McCammon JA, et al. Thalassiolins A-C: New marine-derived inhibitors of HIV cDNA integrase. Bioorg Med Chem 2002; 10: 3619-25.
31. Lerch ML, Faulkner DJ. Unusual polyoxygenated sterols from a Philippines sponge Xestospongia sp. Tetrahedron 2001; 57: 4091-4.
32. Drake RR, Neamati N, Hong H, Pilon AA, Sunthankar P, Hume SD, et al. Identification of a nucleotide binding site in HIV-1 integrase. Proc Natl Acad Sci U S A 1998; 95: 4170-5.
33. Taktakishvili M, Neamati N, Pommier Y, Nair V. Discovery of a nuclease-resistant, non-natural dinucleotide that inhibits HIV-1 integrase. Bioorg Med Chem Lett 2001; 11: 1433-5.
34. Zhang X, Neamati N, Lee YK, Orr A, Brown RD, Whitaker N, et al. Arylisothiocyanate-containing esters of caffeic acid designed as affinity ligands for HIV-1 integrase. Bioorg Med Chem 2001; 9: 1649-57.
35. Neamati N, Lin Z, Karki RG, Orr A, Cowansage K, Strumberg D, et al. Metal-dependent inhibition of HIV-1 integrase. J Med Chem 2002; 45: 5661-70.
36. Pannecouque C, Pluymers W, Van Maele B, Tetz V, Cherepanov P, De Clercq E, et al. New class of HIV integrase inhibitors that block viral replication in cell culture. Curr Biol 2002; 12: 1169-77.
37. Neamati N. Dipyrimidine-based inhibitors of HIV-1 integrase. Expert Opin Invest Drugs 2003; 12: 289-92.
38. Pluymers W, Pais G, Van Maele B, Pannecouque C, Fikkert V, Burke Jr TR, Jr., et al. Inhibition of Human Immunodeficiency Virus Type 1 Integration by Diketo Derivatives. Antimicrob Agents Chemother 2002; 46: 3292-7.
39. Goldgur Y, Craigie R, Cohen GH, Fujiwara T, Yoshinaga T, Fujishita T, et al. Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: a platform for antiviral drug design. Proc Natl Acad Sci U S A 1999; 96: 13040-3.
40. Hazuda DJ, Felock P, Witmer M, Wolfe A, Stillmock K, Grobler JA, et al. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science 2000; 287: 646-50.
41. Pais GC, Zhang X, Marchand C, Neamati N, Cowansage K, Svarovskaia ES, et al. Structure Activity of 3-Aryl-1,3-diketo-Containing Compounds as HIV-1 Integrase Inhibitors. J Med Chem 2002; 45: 3184-94.
42. Grobler JA, Stillmock K, Hu B, Witmer M, Felock P, Espeseth AS, et al. Diketo acid inhibitor mechanism and HIV-1 integrase: implications for metal binding in the active site of phosphotransferase enzymes. Proc Natl Acad Sci U S A 2002; 99: 6661-6.
43. Rice PA, Baker TA. Comparative architecture of transposase and integrase complexes. Nat Struct Biol 2001; 8: 302-7.
44. Melck M, Gellert M. RAG1/2-mediated resolution of transposition intermediates: two pathways and possible consequences. Cell 2000; 101: 625-33.
45. Melek M, Jones JM, O'Dea MH, Pais G, Burke TR, Jr., Pommier Y, et al. Effect of HIV integrase inhibitors on the RAG1/2 recombinase. Proc Natl Acad Sci U S A 2002; 99: 134-7.
46. Buolamwini JK, Assefa H. CoMFA and CoMSIA 3D QSAR and Docking Studies on Conformationally-Restrained Cinnamoyl HIV-1 Integrase Inhibitors:? Exploration of a Binding Mode at the Active Site. J Med Chem 2002; 45: 841-52.
47. Makhija MT, Kulkarni VM. Eigen value analysis of HIV-1 integrase inhibitors. J Chem Inf Comput Sci 2001; 41: 1569-77.
48. Makhija MT, Kulkarni VM. QSAR of HIV-1 integrase inhibitors by genetic function approximation method. Bioorg Med Chem 2002; 10: 1483-97.
49. Guenther S, Nair V. Binding modes of two novel dinucleotide inhibitors of HIV-1 integrase. Bioorg Med Chem Lett 2002, 12: 2233-6.
50. Perryman AL, McCammon JA. AutoDocking dinucleotides to the HIV-1 integrase core domain: Exploring possible binding sites for viral and genomic DNA. J Med Chem 2002; 45: 5624-7.
51. Ni H, Sotriffer CA, McCammon JA. Ordered water and ligand mobility in the HIV-1 integrase-5CITEP complex: a molecular dynamics study. J Med Chem 2001; 44: 3043-7.
52. Neamati N. Structure-based HIV-1 integrase inhibitor design: a future perspective. Expert Opin Invest Drugs 2001; 10: 281-96.
53. Chen IJ, Neamati N, MacKerell AD, Jr. Structure-based inhibitor design targeting HIV-1 integrase. Curr Drug Targets Infect Disord 2002; 2: 217-34.
54. Campiani G, Ramunno A, Maga G, Nacci V, Fattorusso C, Catalanotti B, et al. Non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors: past, present, and future perspectives. Curr Pharm Des 2002; 8(8): 615-57.
55. Carlson HA. Protein flexibility is an important component of structure-based drug discovery. Curr Pharm Des 2002; 8(17): 1571-8.
56. Tarrago-Litvak L, Andreola ML, Fournier M, Nevinsky GA, Parissi V, de Soultrait VR, et al. Inhibitors of HIV-1 reverse transcriptase and integrase: classical and emerging therapeutical approaches. Curr Pharm Des 2002; 8(8): 595-614.