New AZT conjugates as potent anti-HIV agents

Nucleosides, Nucleotides and Nucleic Acids

Volumn 25, Issue 1, 2006, Pages 37-54

  You, Zhengqing ^a   Lee, Henry ^a  

^a FLORIDA A AND M UNIVERSITY   (United States)

Author keywords

2 Imidazolidone 4 carboxylic acid; 2 Pyrrolidone 5 carboxylic acid; Anti HIV; AZT; Prodrug; Steroid; Tetrahydropyrimidinone

Indexed keywords

2 IMIDAZOLIDONE 4 CARBOXYLIC ACID, 3' AZIDO 3' DEOXYTHYMIDIN 5' YL ESTER; 2 PYRROLIDONE 5 CARBOXYLIC ACID, 3' AZIDO 3' DEOXYTHYMIDIN 5' YL ESTER; 3ALPHA ACETYLOXY 5 BETA CHOLANIC ACID, 3' AZIDO 3' DEOXYTHYMIDIN 5' YL ESTER; 4 IMIDAZOLECARBOXYLIC ACID, 3' AZIDO 3' DEOXYTHYMIDIN 5' YL ESTER; 5 BETA CHOLANIC ACID 3,7,12 TRIONE, 3' AZIDO 3' DEOXYTHYMIDIN 5' YL ESTER; 5 BETA CHOLANIC ACID, 3' AZIDO 3' DEOXYTHYMIDIN 5' YL ESTER; 5 HYDROXYTETRAHYDROPYRIMIDIN 2 ONE; CARBOXYLIC ACID DERIVATIVE; CHOLANIC ACID DERIVATIVE; CYCLOPENTANECARBOXYLIC ACID, 3' AZIDO 3' DEOXYTHYMIDIN 5' YL ESTER; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; N BUTYL 2 PYRROLIDONE 5 CARBOXYLIC ACID; N BUTYL 2 PYRROLIDONE 5 CARBOXYLIC ACID, 3' AZIDO 3' DEOXYTHYMIDIN 5' YL ESTER; N METHYL 2 PYRROLIDONE 5 CARBOXYLIC ACID; N METHYL 2 PYRROLIDONE 5 CARBOXYLIC ACID, 3' DIAZO 3' DEOXYTHYMIDIN 5' YL ESTER; N,N' DIBENZYL 5 HYDROXYTETRAHYDROPYRIMIDIN 2 ONE; N,N' DIBENZYL 5 O BENZYLTETRAHYDROPYRIMIDIN 2 ONE; N,N' DIBENZYLTETRAHYDROPYRIMIDIN 2 ON 5 YL 3' DIAZO 3' DEOXYTHYMIDIN 5'4 YL SUCCINATE; N,N' DIMETHYL 2 IMIDAZOLIDONE 4 CARBOXYLIC ACID; N,N' DIMETHYL 2 IMIDAZOLIDONE 4 CARBOXYLIC ACID, 3' DIAZO 3' DEOXYTHYMIDIN 5' YL ESTER; N,N' DIPHENYL 5 HYDROXYTETRAHYDROPYRIMIDIN 2 ONE; N,N' DIPHENYL 5 METHYLENETETRAHYDROPYRIMIDIN 2 ONE; N,N' DIPHENYLTETRAHYDROPYRIMIDIN 2 ON 5 YL 3' DIAZO 3' DEOXYTHYMIDIN 5' YL SUCCINATE; PYROGLUTAMIC ACID; RNA DIRECTED DNA POLYMERASE INHIBITOR; SUCCINIC ACID DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZIDOVUDINE; ZIDOVUDINE DERIVATIVE;

ARTICLE; CELL LINE; CYTOTOXICITY; DRUG ACTIVITY; DRUG POTENCY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS; NONHUMAN;

ANTI-HIV AGENTS; CELL LINE; MOLECULAR STRUCTURE; ZIDOVUDINE;

EID: 33644815492     PISSN: 15257770     EISSN: 15322335     Source Type: Journal    
DOI: 10.1080/15257770500377789     Document Type: Article

References (22)

1. Mitsuya, H.; Weinhold, K.J.; Furman, P.A.; St. Clair, M.H.; Nusinoff-Lehrman, S.; Gallo, R.C.; Bolognesi, D.; Barry, D.W.; Broder, S. 3′-Azido-3′-deoxythymidine (BW A509U): An antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc. Natl. Acad. Sci. U.S.A. 1985, 82(20), 7096-7100.
2. Richman, D.D.; Fischl, M.A.; Grieco, M.H.; Gottlieb, M.S.; Volberding, P.A.; Laskill, O.L.; Leedom, J.M.; Groogman, J.E.; Mildvan, D.; Schooley, R.T.; Jackson, G.G.; Durack, D.T.; Phil, D.; King, D. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. N. Engl. J. Med. 1987, 317(4), 185-191.
3. Mitsuya, H.; Broder, S. Strategies for antiviral therapy in AIDS. Nature (London) 1987, 325(6107), 773-778.
4. Fischl, M.A.; Richman, D.D.; Grieco, M.H.; Gottlieb, M.S.; Volberding, P.A.; Laskon, O.L.; Leedom, J.M.; Grooman, J.E.; Mildvan, D.; Hirsch, M.S.; Jackson, G.G.; Durack, D.T.; Musinoff-Lehrman, S. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. N. Engl. J. Med. 1987, 317(4), 192-197.
5. De Clercq, E. Perspectives for the chemotherapy of AIDS. Anticancer Res. 1987, 7(5B), 1023-1038.
6. Zimmerman, T.P.; Mahony, W.B.; Prus, K.L. 3′-Azido-3′- deoxythymidine: An unusual nucleoside analogue that permeates the membrane of human erythrocytes and lmphocytes by non-facilitated diffusion. J. Biol. Chem. 1987, 262(12), 5748-5754.
7. Dessolin, J.; Galea, P.; Vlieghe, P.; Chermann, J.-C.; Kraus, J.-L. New bicyclam-AZT conjugates: Design, synthesis, anti-HIV evaluation, and their interaction with CXCR-4 coreceptor. J. Med. Chem. 1999, 42(2), 229-241.
8. Aggarwal, S.K.; Gogu, S.R.; Rangan, S.R.S.; Agrawal, K.C. Synthesis and biological evaluation of zidovudine. J. Med. Chem. 1990, 33(5), 1505-1510.
9. Sharma, A.P.; Ollapally, A.P.; Lee, H.J. Synthesis and anti-HIV activity of prodrugs of azidothymidine. Antiviral Chem. Chemother. 1993, 4(2), 93-96.
10. Meier, C.; Knispel, T.; De Clercq, E.; Balzarini, J. cycloSal- pronucleotides of 2′,3′-dieoxyadenosine and 2′,3′- dideoxy-2′,3′-didehydroadenosine: Synthesis and antiviral evaluation of a highly efficient nucleotide delivery system. J. Med. Chem. 1999, 42(9), 1604-1614.
11. Hong, C.I.; Nechaev, A.; Kirisits, A.J.; Vig, R.; West, C.R.; Manouilov, K.K.; Chu, C.K. Nucleoside conjugates. 15. Synthesis and biological activity of anti-HIV nucleoside conjugates of ether and thioether phospholipids. J. Med. Chem. 1996, 39, 1771.
12. Namane, A.; Gouyette, C.; Fillion, M.-P.; Fillion, G.; Huynh-Dinh, T. Improved brain delivery of AZT using a glycosyl phosphotriester prodrug. J. Med. Chem. 1992, 35(16), 3039-3044.
13. Vlieghe, P.; Clerc, T.; Pannecouque, C.; Witvrouw, M.; De Clercq, E.; Salles, J.-P.; Kraus, J.-L. New 3′-Azido-3′-deoxythymidin-5′- yl O-(4-hydroxyalkyl or -alkenyl or -alkylepoxide) carbonate prodrugs: Synthesis and anti-HIV evaluation. J. Med. Chem. 2001, 44(18), 3014-3021.
14. Lee, H.J.; Soliman, M.R.I. Anti-inflammatory steroids without pituitary-adrenal suppression. Science 1982, 215(4535), 989-991.
15. Rosner, W. Plasma steroid-binding proteins. Endocrinol. Metab. Clin. North Am. 1991, 20(4), 697.
16. You, Z.; Mian, A.M.; Agarwal, R.P.; Lee, H.J. Synthesis, anti-HIV, and cytotoxic activity of new AZT conjugates of steroid acids. Nucleos. Nucleot. Nucl. Acids 2003, 22(11), 2049-2060.
17. Matsumoto, H.; Hamawaki, T.; Ota, H.; Kimura, T.; Goto, T.; Sano, K.; Hayashi, Y.; Kiso, Y. "Double-drugs" - A new class of prodrug form of an HIV protease inhibitor conjugated with a reverse transcriptase inhibitor by a spontaneously cleavable linker. Bioorganic & Med. Chem. Letters 2000, 10(11), 1227.
18. De Lucca, G.V.; Liang, J.; Aldrich, P.E.; Calabrese, J.; Cordova, B.; Klabe, R.M.; Rayner, M.M.; Chang, C.-H. Design, synthesis, and evaluation of tetrahydropyrimidinones as an example of a general approach to nonpeptide HIV protease inhibitors. J. Med. Chem. 1997, 40(11), 1707-1709.
19. Fyles, T.M.; James, T.D.; Pryhitka, A.; Zojaji, M. Assembly of ion channel mimics from a modular construction set. J. Org. Chem. 1993, 58, 7456-7468.
20. Hori, H.; Nishida, Y.; Ohrui, H.; Meguro, H. Regioselective de-O-benzylation with Lewis acids. J. Org. Chem. 1989, 54, 1346-1353.
21. Weislow, O.S.; Kiser, R.; Fine, D.L.; Bader, J.; Shoemaker, R.H.; Boyd, M.R. New soluble-formazan assay for HIV-1 cytopathic effects: Application to high-flux screening of synthetic and natural products for AIDS-antiviral activity. J. Natl. Cancer Inst. 1989, 81(8), 577-586.
22. 50 values of AZT, as is suggested by the NCI, should be obtained from previously published articles such as reference 21.