Department of Pharmaceutical Chemistry, Marmara University, Haydarpaşa, İstanbul, Turkey.
Arch Pharm (Weinheim). 2013 Feb;346(2):140-53. doi: 10.1002/ardp.201200311. Epub 2012 Dec 20.
In accordance with our antiviral drug development attempt, acylhydrazone derivatives bearing amino acid side chains were synthesized for the evaluation of their antiviral activity against various types of viruses. Among these compounds, 8(S) , 11(S) , and 12(S) showed anti-HIV-1 activity with a 50% inhibitory concentration (IC(50)) =123.8 µM (selectivity index, SI>3), IC(50) =12.1 µM (SI>29), IC(50) =17.4 µM (SI>19), respectively. Enantiomers 8(R) , 11(R) , and 12(R) were inactive against the HIV-1 strain III(B) . Hydrazones 8(S) , 11(S) , and 12(S) which were active against HIV-1 wild type showed no inhibition against a double mutant NNRTI-resistant strain (K103N;Y181C). Molecular docking calculations of R- and S-enantiomers of 8, 11, and 12 were performed using the hydrazone-bound novel site of HIV-1 RT.
根据我们的抗病毒药物开发尝试，我们合成了带有氨基酸侧链的酰腙衍生物，以评估它们对各种类型病毒的抗病毒活性。在这些化合物中，化合物 8(S)、11(S)和 12(S)对 HIV-1 表现出抗活性，半数抑制浓度 (IC(50))分别为 123.8 μM (选择性指数，SI>3)、12.1 μM (SI>29)和 17.4 μM (SI>19)。对 HIV-1 株 III(B)，非对映异构体 8(R)、11(R)和 12(R)没有活性。对 HIV-1 野生型有活性的腙 8(S)、11(S)和 12(S)对双重突变 NNRTI 耐药株 (K103N;Y181C)没有抑制作用。使用 HIV-1 RT 的结合新型位点，对 R-和 S-对映异构体 8、11 和 12 进行了分子对接计算。
