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).

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