Stampidine is a potential nonspermicidal broad-spectrum anti-human immunodeficiency virus microbicide

Fertility and Sterility

Volumn 81, Issue SUPPL. 1, 2004, Pages 831-841

  D'Cruz, Osmond J ^a,b   Uckun, Fatih M ^a  

^a PARKER HUGHES INSTITUTE   (United States)

^b Paradigm Pharmaceuticals   (United States)

Author keywords

AIDS HIV; Intravaginal; Microbicide; Rabbit; Sperm; Stavudine d4T; Thermoreversible gel

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; MICROBICIDE; STAMPIDINE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELL VIABILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOTOXICITY; DRUG EFFECT; EPITHELIUM CELL; FEMALE; GESTATIONAL AGE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; KINEMATICS; MALE; NIDATION; NONHUMAN; PREGNANCY RATE; PREIMPLANTATION EMBRYO; PRIORITY JOURNAL; RABBIT; SPERMATOZOON MOTILITY; SPERMATOZOON PENETRATION; UTERINE CERVIX EPITHELIUM; UTERINE CERVIX MUCUS;

ANIMALS; ANTI-HIV AGENTS; BIOMECHANICS; CATTLE; CERVIX MUCUS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG STABILITY; FEMALE; FERTILITY; GELS; HIV; HUMANS; HYDROGEN-ION CONCENTRATION; MALE; MUCOUS MEMBRANE; PREGNANCY; RABBITS; SPERM MOTILITY; SPERMATOZOA; STAVUDINE; THYMIDINE MONOPHOSPHATE; VAGINA;

EID: 1542513385     PISSN: 00150282     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.fertnstert.2003.08.037     Document Type: Article

References (44)

1. United Nations Program on HIV/AIDS. Report on global HIV/AIDS epidemic. December 2001. Accessed at http://www.unaids.org
2. NIAID Fact Sheet. HIV Infection in Women, May 2003. Accessed at http://www.niaid.nih.gov/factsheets/womenhiv.htm. HIV/AIDS statistics, December 2002. Accessed at http://biodefense.niaid.nih.gov/factsheets/aidsstat.htm
3. CBS News: Women half of 42 million world HIV victims: UN. November 2002. Accessed at http://www.cbc.ca/stories/2002/11/26/aids021126 0
4. Uckun F.M., D'Cruz O.J. Prophylactic contraceptives for HIV/AIDS. Hum Reprod Update. 5:1998;506-514.
5. Turpin J.A. Considerations and development of topical microbicides to inhibit the sexual transmission of HIV. Expert Opin Invest Drugs. 11:2002;1077-1097.
6. Friedland G.H., Klein R.S. Transmission of the human immunodeficiency virus. N Engl J Med. 317:1987;1125-1135.
7. Brown D. Study finds drug-resistant HIV in half of infected patients. Washington Post News Report 2001; December 19:A02.
8. Susman E. Many HIV patients carry mutated drug-resistant strains. Lancet. 359:2002;49.
9. Yozviak J.L., Doerfler R.E., Woodward W.C. Effectiveness and tolerability of nevirapine, stavudine, and lamivudine in clinical practice. HIV Clin Trials. 2:2001;474-476.
10. Balzarini J., Karlsson A., Aquaro S., Perno C.F., Cahard D., Naesens L., et al. Mechanism of anti-HIV action of masked alaninyl d4T-MP derivatives. Proc Natl Acad Sci USA. 93:1996;7295-7299.
11. Balzarini J., Egberink H., Hartmann K., Cahard D., Vahlenkamp T., Thormar H., et al. Antiretrovirus specificity and intracellular metabolism of 2′,3′-didehydro-2′3′-dideoxythymidine (stavudine) and its 5′-monophosphate triester prodrug So324. Mol Pharmacol. 50:1996;1207-1213.
12. Vig R., Venkatachalam T.K., Uckun F.M. D4T-5′[p-bromo- phenylmethoxyalaninyl phosphate] as a potent and non-toxic anti-HIV agent. Antivir Chem Chemother. 9:1998;445-448.
13. Uckun F.M., Samuel P., Qazi S., Chen C., Pendergrass S., Venkatachalam T.K. Effects of aryl substituents on the anti-HIV activity of the arylphosphoramidate derivatives of stavudine. Antivir Chem Chemother. 13:2002;197-203.
14. Venkatachalam T.K., Tai H.-L., Vig R., Chen C.-L., Jan S.-T., Uckun F.M. Enhancing effects of a mono-bromo substitution at the para position of the phenyl moiety on the metabolism and anti-HIV activity of d4T-phenyl methoxyalaninyl phosphate derivatives. Bioorg Med Chem Lett. 8:1998;3121-3126.
15. Uckun F.M., Pendergrass S., Venkatachalam T.K., Qazi S., Richman D. Stampidine is a potent inhibitor of zidovudine- and nucleoside analog reverse transcriptase inhibitor-resistant primary clinical human immunodeficiency virus type 1 isolates with thymidine analog mutations. Antimicrob Agents Chemother. 46:2002;3613-3616.
16. Uckun FM, Pendergrass S, Qazi S, Venkatachalam TK. In vitro activity of stampidine against primary clinical human immunodeficiency virus isolates. Arznimittel Forschung/Drug Research Drug 2004;54:69-77
17. Uckun F.M., Qazi S., Pendergrass S., Lisowski E., Waurzyniak B., Chen C.L., et al. In vivo toxicity, pharmacokinetics, and anti-human immunodeficiency virus activity of stavudine-5′-(p-bromophenyl methoxyalaninyl phosphate) (stampidine) in mice. Antimicrob Agents Chemother. 46:2002;3428-3436.
18. Uckun F.M., Chen C.L., Samuel P., Pendergrass S., Venkatachalam T.K., Waurzyniak B., et al. In vivo antiretroviral activity of stampidine in chronically feline immunodeficiency virus-infected cats. Antimicrob Agents Chemother. 47:2003;1233-1240.
19. Uckun FM, Chen C, Lisowski E, Mitcheltree G, Venkatachalam T, Erbeck D, et al. Toxicity and pharmacokinetics of stampidine in mice and rats. Arznimittel Forschung/Drug Res 2003;53:357-67
20. Chen C.L., Venkatachalam T.K., Zhu Z.H., Uckun F.M. In vivo pharmacokinetics and metabolism of anti-human immunodeficiency virus agent D4T-5′-[p-bromophenyl methoxyalaninyl phosphate](SAMPIDINE) in mice. Drug Metab Dispos. 29:2001;1035-1041.
21. Chen C.L., Yu G., Venkatachalam T.K., Uckun F.M. Metabolism of stavudine-5′-[p-bromophenyl methoxyalaninyl phosphate], stampidine, in mice, dogs, and cats. Drug Metab Dispos. 30:2002;1523-1531.
22. D'Cruz O.J., Venkatachalam T.K., Zhu Z., Shih M.-J., Uckun F.M. Bromo-methoxy and aryl phosphate derivatives of azidothymidine are dual-function spermicides with potent anti-HIV activity. Biol Reprod. 59:1998;503-515.
23. D'Cruz O.J., Zhu Z., Yiv S.H., Chen C.-L., Uckun F.M. Synthesis, characterization, and preclinical formulation of a dual-action phenyl phosphate derivative of bromo-methoxy zidovudine (compound WHI-07) with potent anti-HIV and spermicidal activities. Mol Hum Reprod. 5:1999;421-432.
24. D'Cruz O.J., Uckun F.M. Novel derivatives of phenethyl-5- bromopyridylthiourea and dihydroalkoxybenzyloxopyrimidine are dual-function spermicides with potent anti-HIV activity. Biol Reprod. 60:1999;1419-1428.
25. D'Cruz O.J., Venkatachalam T.K., Uckun F.M. Novel thiourea compounds as dual-function microbicides. Biol Reprod. 63:2000;196-205.
26. D'Cruz O.J., Venkatachalam T.K., Mao C., Qazi S., Uckun F.M. Structural requirements for potent anti-human immunodeficiency virus (HIV) and sperm-immobilizing activities of cyclohexenyl thiourea and urea non-nucleoside inhibitors of HIV-1 reverse transcriptase. Biol Reprod. 67:2002;1959-1974.
27. D'Cruz O.J., Dong Y., Uckun F.M. Apoptosis-inducing oxovanadium(IV) complexes of 1,10-phenanthroline against human ovarian cancer. Anticancer Drugs. 11:2000;849-858.
28. Qazi S., Samuel N.K., Venkatachalam T.K., Uckun F.M. Evaluating dissolution profiles of an anti-HIV agent using ANOVA and non-linear regression models in JMP software. Int J Pharm. 252:2003;27-39.
29. D'Cruz O.J., Uckun F.M. Effect of pretreatment of semen with pokeweed antiviral protein on pregnancy outcome in the rabbit model. Fertil Steril. 76:2001;830-833.
30. Eckstein P., Jackson M.C., Millman N., Sobrero A.J. Comparison of vaginal tolerance tests of spermicidal preparations in rabbits and monkeys. J Reprod Fertil. 20:1969;85-93.
31. De Geyter C., Bals-Pratsch M., Doeren M., Yeung C.H., Grunert J.H., Bordt J., et al. Human and bovine cervical mucus penetration as a test of sperm function for in-vitro fertilization. Hum Reprod. 3:1988;948-954.
32. Quayle A.J., Xu C., Mayer K.H., Anderson D.J. T lymphocytes and macrophages, but not motile spermatozoa, are a significant source of human immunodeficiency virus in semen. J Infect Dis. 176:1997;960-968.
33. Zhang H., Dornadula G., Beumont M., Livornese L. Jr, Van Uitert B., Henning K., et al. Human immunodeficiency virus type 1 in the semen of men receiving highly active antiretroviral therapy. N Engl J Med. 339:1998;1803-1809.
34. Scofield V.L. Sperm as infection-potentiating cofactors in HIV transmission. J Reprod Immunol. 41:1998;359-372.
35. Piomboni P., Baccetti B. Spermatozoa as a vehicle for HIV-1 and other viruses. Mol Reprod Dev. 56:2000;238-242.
36. Hu D.J., Dondero T.J., Rayfield M.A., George J.R., Schochetman G., Jaffe H.W., et al. The emerging genetic diversity of HIV the importance of global surveillance for diagnostics, research and prevention. JAMA. 275:1996;210-216.
37. Kuiken C.L., Foley B., Hahn B. Human retroviruses and AIDS: a compilation and analysis of nucleic acid and amino acid sequences. 1999;Los Alamos National Laboratory, Los Alamos, NM.
38. Palmer S., Alaeus A., Albert J., Cox S. Drug susceptibility of subtypes A,B,C,D, and E human immunodeficiency virus type 1 isolates. AIDS Res Hum Retroviruses. 14:1998;157-162.
39. Miller M.D., Margot N.A., Lamy P.D., Fuller M.D., Anton K.E., Mulato A.S., et al. Adefovir and tenofovir susceptibilities of HIV-1 after 24 to 48 weeks of adefovir dipivoxil therapy genotypic and phenotypic analyses of study GS-96-408. J Acquir Immune Defic Syndr. 27:2001;450-458.
40. D'Cruz O.J., Uckun F.M. Pre-clinical safety evaluation of novel nucleoside analogue-based dual-function microbicides (WHI-05 and WHI-07). J Antimicrob Chemother. 50:2002;793-803.
41. Quinn T.C., Wawer M.J., Sewankambo N., Serwadda D., Li C., Wabwire-Mangen F., et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med. 342:2000;921-929.
42. Semprini A.E., Levi-Setti P., Bozzo M., Ravizza M., Taglioretti A., Sulpizio P., et al. Insemination of HIV-negative women with processed semen of HIV-positive partners. Lancet. 340:1992;1317-1319.
43. Marina S., Marina F., Alcolea R., Exposito R., Huguet J., Nadal J., et al. Human immunodeficiency virus type 1-serodiscordant couples can bear healthy children after undergoing intrauterine insemination. Fertil Steril. 70:1998;35-39.
44. Vernazza P.L., Eron J.J., Fiscus S.A., Cohen M.S. Sexual transmission of HIV infectiousness and prevention. AIDS. 13:1999;155-166.