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


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


Jul 22, 1992·JAMA : the Journal of the American Medical Association·J KreissT R Fleming
Feb 1, 1992·AIDS Research and Human Retroviruses·E De Clercq
Jul 1, 1991·Sexually Transmitted Diseases·S NiruthisardS Chutivongse
Sep 28, 1990·Science·H MitsuyaS Broder
Jan 31, 1991·The New England Journal of Medicine·W C Greene
Sep 14, 1989·Nature·N Bosworth, P Towers
Jan 1, 1988·American Journal of Public Health·P J Feldblum, J A Fortney
Mar 1, 1984·Toxicology Letters·L Tryphonas, H S Buttar
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·S J SmerdonT A Steitz
Apr 1, 1995·Nature Structural Biology·J RenD Stuart
Apr 1, 1995·Genitourinary Medicine·S S WeirP J Feldblum
May 1, 1993·International Journal of STD & AIDS·R E RoddyJ A Fortney
May 28, 1993·Science·R A Weiss
Apr 1, 1997·International Journal of STD & AIDS·S K HiraJ C Thomas
Feb 11, 1998·Journal of Medicinal Chemistry·K DanelC Nielsen
Apr 3, 1998·Sexually Transmitted Diseases·R L Cook, M J Rosenberg
Apr 3, 1998·Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association·M K StaffordV S Kitchen
Jun 12, 1998·Biology of Reproduction·O J D'CruzF M Uckun


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

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