Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
Eur J Med Chem. 2014 Jun 10;80:101-11. doi: 10.1016/j.ejmech.2014.04.027. Epub 2014 Apr 12.
New indolylarylsulfone HIV-1 NNRTIs were synthesized to evaluate unexplored substitutions of the benzyl/phenylethyl group linked at the indole-2-carboxamide. Against the NL4-3 HIV-1 WT strain, 17 out 20 compounds were superior to NVP and EFV. Several compounds inhibited the K103N HIV-1 mutant strain at nanomolar concentration and were superior to EFV. Some derivatives were superior to EFV against the Y181C and L100I HIV-1 mutant strains. Against the NL4-3 HIV-1 strain, the enantiomers 24 and 25 showed small differences of activity. In contrast, 24 turned out significantly more potent than 25 against the whole panel of mutant HIV-1 strains. The docking studies suggested that the difference in the observed inhibitory activities of 24 and 25 against the K03N mutation could be due to a kinetic rather than affinity differences.
新的吲哚芳基砜 HIV-1 NNRTIs 被合成以评估与吲哚-2-甲酰胺相连的苄基/苯乙基基团的未探索取代。针对 NL4-3 HIV-1 WT 株，20 个化合物中有 17 个优于 NVP 和 EFV。几种化合物以纳摩尔浓度抑制 K103N HIV-1 突变株，优于 EFV。一些衍生物对 Y181C 和 L100I HIV-1 突变株的抑制作用优于 EFV。针对 NL4-3 HIV-1 株，对映体 24 和 25 表现出活性的微小差异。相比之下，24 对整个突变 HIV-1 株的活性明显强于 25。对接研究表明，观察到的 24 和 25 对 K03N 突变的抑制活性差异可能是由于动力学而非亲和力差异所致。
