PMID: 10859260Jun 22, 2000

Novel thiourea compounds as dual-function microbicides

Biology of Reproduction
Osmond J D'CruzFatih M Uckun

Abstract

Sexually active women represent the fastest growing human immunodeficiency virus (HIV)/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 previously reported the synthesis of novel nonnucleoside inhibitors (NNIs) of HIV-1 reverse transcriptase with sperm-immobilizing activity (SIA). To gain further insight into the structure-function relationship controlling these two properties of NNIs, we have rationally designed and synthesized 30 novel thiourea compounds and examined them for dual-function, anti-HIV and spermicidal activity. Twelve of the 30 thiourea compounds exhibited potent anti-HIV activity in the nanomolar range (IC(50) = <1-9 nM). Nine of the 30 thiourea derivatives exhibited both anti-HIV and spermicidal activity. Among the phenyl ring-containing thioureas, the 2-fluoro (HI-240) -substituted and 2-chloro (HI-253) -substituted derivatives exhibited potent anti-HIV activity (IC(50) = <1 nM) with SIA (EC(50) = 70 microM and 147 microM). Among the alicyclic ring-containing thioureas, the 5-bromo (HI-346) and 5-chloro (HI-445) functionalized cyclohexenyl ring-substituted th...Continue Reading

References

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
May 1, 1992·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·P TamuelviciusC Streffer
Jul 1, 1991·Sexually Transmitted Diseases·S NiruthisardS Chutivongse
Sep 28, 1990·Science·H MitsuyaS Broder
Jan 2, 1991·JAMA : the Journal of the American Medical Association·T M HootonW E Stamm
Jan 31, 1991·The New England Journal of Medicine·W C Greene
Jun 7, 1991·MMWR. Morbidity and Mortality Weekly Report·Centers for Disease Control (CDC)
Sep 14, 1989·Nature·N Bosworth, P Towers
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
Jan 1, 1995·International Journal of Gynaecology and Obstetrics : the Official Organ of the International Federation of Gynaecology and Obstetrics·J K MatiP M Tukei
Apr 1, 1995·Genitourinary Medicine·S S WeirP J Feldblum
Mar 1, 1995·The Veterinary Clinics of North America. Small Animal Practice·S C Kerwin
Nov 27, 1993·Lancet·J M LangeP Piot
Nov 1, 1994·The Journal of Cell Biology·B BaccettiA Massacesi
Jun 1, 1994·American Journal of Public Health·M Potts
May 1, 1993·International Journal of STD & AIDS·R E RoddyJ A Fortney
Jul 13, 1996·Lancet·T C Quinn
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·Osmond J D'CruzFatih M Uckun
Aug 14, 1998·Molecular Human Reproduction·Osmond J D'CruzFatih M Uckun
Dec 3, 1999·Human Reproduction Update·Fatih M Uckun, Osmond J D'Cruz

Citations

Nov 13, 2001·Contraception·Osmond J D'Cruz, Fatih M Uckun
Feb 13, 2001·Fertility and Sterility·Osmond J D'Cruz, Fatih M Uckun
Sep 6, 2002·Bioorganic & Medicinal Chemistry·Yue-Ling WongRichard D Gandour
Aug 13, 2004·Biology of Reproduction·Osmond J D'CruzFatih M Uckun
Jan 20, 2004·AAPS PharmSciTech·Osmond J D'CruzFatih M Uckun
Dec 16, 2005·AAPS PharmSciTech·Osmond J D'CruzFatih M Uckun
Aug 2, 2002·Expert Opinion on Investigational Drugs·Jim A Turpin
Feb 2, 2006·The European Journal of Contraception & Reproductive Health Care : the Official Journal of the European Society of Contraception·Gopal Gupta
Jun 10, 2004·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Osmond J D'CruzFatih M Uckun
Mar 17, 2004·Fertility and Sterility·Osmond J D'Cruz, Fatih M Uckun
Feb 13, 2001·Toxicology and Applied Pharmacology·Osmond J D'Cruz, Fatih M Uckun
Jan 11, 2003·Biotechnology & Genetic Engineering Reviews·Walter MaglianiLuciano Polonelli
Nov 13, 2009·European Journal of Medicinal Chemistry·Lalit KumarGopal Gupta
Oct 25, 2006·Journal of Enzyme Inhibition and Medicinal Chemistry·Osmond J D'Cruz, Fatih M Uckun
May 4, 2016·Journal of Inorganic Biochemistry·Taracad K VenkatachalamDavid C Reutens
Jun 18, 2004·Toxicologic Pathology·Osmond J D'CruzFatih M Uckun
Feb 7, 2019·Biomedical Materials·Bhuvaneshwaran SubramanianSujoy K Guha
Jan 25, 2006·The Journal of Antimicrobial Chemotherapy·Osmond J D'Cruz, Fatih M Uckun

Related Concepts

HI 445
HI 253
Cervix Uteri
Medicinal Plants Testing, Preclinical
Pyridines
Sperm Motility
Vaginal Spermicides
Structure-Activity Relationship
Thiourea
Vagina

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Alzheimer's Disease: MS4A

Variants within the membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease in genome-wide association studies. Here is the latest research on Alzheimer's disease and MS4A.

Pediculosis pubis

Pediculosis pubis is a disease caused by a parasitic insect known as Pthirus pubis, which infests human pubic hair, as well as other areas with hair including eye lashes. Here is the latest research.

Rh Isoimmunization

Rh isoimmunization is a potentially preventable condition that occasionally is associated with significant perinatal morbidity or mortality. Discover the latest research on Rh Isoimmunization here.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells. It also follows CRISPR-Cas9 approaches to generating genetic mutants as a means of understanding the effect of genetics on phenotype.

Enzyme Evolution

This feed focuses on molecular models of enzyme evolution and new approaches (such as adaptive laboratory evolution) to metabolic engineering of microorganisms. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Pharmacology of Proteinopathies

This feed focuses on the pharmacology of proteinopathies - diseases in which proteins abnormally aggregate (i.e. Alzheimer’s, Parkinson’s, etc.). Discover the latest research in this field with this feed.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.