PMID: 10330101May 18, 1999

Novel derivatives of phenethyl-5-bromopyridylthiourea and dihydroalkoxybenzyloxopyrimidine are dual-function spermicides with potent anti-human immunodeficiency virus activity

Biology of Reproduction
O J D'Cruz, F M Uckun

Abstract

Sexually active women represent the fastest growing HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) risk group. In an effort to develop a vaginal microbicidal contraceptive potentially capable of preventing HIV transmission as well as providing fertility control, we have synthesized novel non-nucleoside inhibitors (NNIs) of HIV-1 reverse transcriptase (RT) and examined them for dual-function anti-HIV and spermicidal activity. Structure-based drug design by use of a computer docking procedure for the NNI binding pocket generated from nine RT-NNI crystal structures led to the synthesis of three novel NNIs: N-[2-(2, 5-dimethoxyphenethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (D-PBT); N-[2-(2-fluorophenethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (F-PBT); and 5-isopropyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-on e (S-DABO). The anti-HIV activity of these NNIs was compared with that of trovirdine and virucidal/spermicide, nonoxynol-9 (N-9), by measuring viral RT activity and p24 antigen production as markers of viral replication using HTLVIIIB-infected human peripheral blood mononuclear cells (PBMCs). The effects on sperm motion kinematics and sperm membrane integrity were examined by computer-assi...Continue Reading

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Citations

Feb 13, 2001·Fertility and Sterility·O J D'Cruz, F M Uckun
Jun 29, 2011·Antimicrobial Agents and Chemotherapy·Ashish JainG Gupta
Jan 20, 2004·AAPS PharmSciTech·O J D'CruzF M Uckun
Aug 2, 2002·Expert Opinion on Investigational Drugs·Jim A Turpin
Jun 22, 2000·Biology of Reproduction·O J D'CruzF M Uckun
Oct 19, 2007·Bioorganic & Medicinal Chemistry·Amira ZairiKhaled Hani
Oct 25, 2006·Journal of Enzyme Inhibition and Medicinal Chemistry·O J D'Cruz, F M Uckun
Jun 18, 2004·Toxicologic Pathology·O J D'CruzF M Uckun
Feb 7, 2019·Biomedical Materials·Bhuvaneshwaran SubramanianSujoy K Guha
Jan 25, 2006·The Journal of Antimicrobial Chemotherapy·O J D'Cruz, F M Uckun

Related Concepts

5-isopropyl-2-((methylthiomethyl)thio)-6-(benzyl)pyrimidin-4(1H)-one
HI 240
N-(2-(2,5-dimethoxyphenethyl))-N'-(2-(5-bromopyridyl))thiourea
Acquired Immunodeficiency Syndrome
Plasma Membrane
Computers, Digital
Synthetic Detergent
Pyridines
Pyrimidones
Sexually Transmitted Diseases

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