PMID: 7539917Jun 6, 1995Paper

Suppression of the breakthrough of human immunodeficiency virus type 1 (HIV-1) in cell culture by thiocarboxanilide derivatives when used individually or in combination with other HIV-1-specific inhibitors (i.e., TSAO derivatives)

Proceedings of the National Academy of Sciences of the United States of America
J BalzariniA Karlsson

Abstract

Five structurally related thiophene and furane analogues of the oxathiin carboxanilide derivative NSC 615985 (UC84) (designated UC10, UC68, UC81, UC42, and UC16) were identified as potent inhibitors of HIV-1 replication in cell culture and HIV-1 reverse transcriptase activity. These compounds were markedly active against a series of mutant HIV-1 strains, containing the Leu-100-->Ile, Val-106-->Ala, Glu-138-->Lys, or Tyr-181-->Cys mutations in their reverse transcriptase. However, the thiocarboxanilide derivatives selected for mutations at amino acid positions 100 (Leu-->Ile), 101 (Lys-->Ile/Glu), 103 (Lys-->Thr/Asp) and 141 (Gly-->Glu) in the HIV-1 reverse transcriptase. The compounds completely suppressed HIV-1 replication and prevented the emergence of resistant virus strains when used at 1.3-6.6 microM--that is, 10- to 25-fold lower than the concentration required for nevirapine and bis(heteroaryl)piperazine (BHAP) U90152 to do so. If UC42 was combined with the [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"- oxathiole-2",2"-dioxide)]-beta-D-pentofuranosyl (TSAO) derivative of N3-methylthymine (TSAO-m3T), virus breakthrough could be prevented for a much longer time, and at much lower concentrations, than i...Continue Reading

References

Aug 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J P BaderM R Boyd
Dec 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·D RichmanJ Griffin

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Citations

Jan 1, 1996·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·E De Clercq
Jun 27, 2000·Antiviral Research·M WitvrouwK Andries
Sep 3, 2003·Bioorganic & Medicinal Chemistry Letters·Marina Udier-BlagovićWilliam L Jorgensen
May 1, 1997·Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association·J BalzariniK Uberla
Oct 3, 2013·PloS One·Hartmut M Hanauske-AbelMichael B Mathews
Jul 2, 2005·Expert Opinion on Emerging Drugs·M L AndreolaM Legraverend
Oct 23, 1997·Clinical Microbiology Reviews·E De Clercq

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