Buemi Maria Rosa, Gitto Rosaria, Ielo Laura, Pannecouque Christophe, De Luca Laura
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Palatucci, 13, I-98168 Messina, Italy.
Department of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.
Bioorg Med Chem. 2020 Apr 15;28(8):115431. doi: 10.1016/j.bmc.2020.115431. Epub 2020 Mar 17.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent potent anti-HIV agents targeting HIV-1 reverse transcriptase (RT), a crucial enzyme for the viral life cycle. We have previously identified a series of NNRTIs bearing a 2,3-diaryl-1,3-thiazolidin-4-one core and some compounds proved to be effective in inhibiting HIV-1 replication at micromolar concentration. As a continuation in this research work we report the design, the synthesis and the structure-activity relationship studies of a further series of 3-(1,3,4-thiadiazol-2-yl)thiazolidin-4-one derivatives containing an arylthioacetamide group as pharmacophoric structural requirement for binding to the RT catalytic area. The new compounds proved to be effective to inhibit RT activity at micromolar concentrations. Finally, docking studies were carried out in order to rationalize the biological results of the new synthesized inhibitors.
非核苷类逆转录酶抑制剂（NNRTIs）是一类针对HIV-1逆转录酶（RT）的强效抗HIV药物，RT是病毒生命周期中的关键酶。我们之前已鉴定出一系列具有2,3-二芳基-1,3-噻唑烷-4-酮核心结构的NNRTIs，部分化合物在微摩尔浓度下可有效抑制HIV-1复制。作为该研究工作的延续，我们报道了另一系列含有芳硫基乙酰胺基团作为与RT催化区域结合的药效结构要求的3-(1,3,4-噻二唑-2-基)噻唑烷-4-酮衍生物的设计、合成及构效关系研究。新化合物在微摩尔浓度下可有效抑制RT活性。最后，进行了对接研究以阐释新合成抑制剂的生物学结果。
