Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, China.
Department of Cancer Center, Shandong University, Jinan 250117, China.
Molecules. 2022 Nov 3;27(21):7538. doi: 10.3390/molecules27217538.
In this study, privileged boronic acid ester was introduced into the right wing of etravirine (ETR) to obtain a series of novel boronate-containing derivatives. These newly synthesized derivatives were evaluated for their anti-HIV potency in MT-4 cells using the MTT method, and their inhibitory activity to HIV-1 reverse transcriptase (RT) was assayed by the ELISA method. Most of the synthesized compounds displayed promising antiviral activity against the wild-type and a wide range of HIV-1 mutant strains. In particular, exhibited the most potent activity against the wild-type and a panel of single mutations (L100I, K103N, Y181C, and E138K) with EC values ranging from 0.005 to 0.648 μM, which were much superior to those of nevirapine (EC = 0.151 μM). Moreover, turned out to be an effective inhibitor against the double-mutant strains F227L + V106A and RES056 with EC values of 3.21 and 2.30 μM, respectively. RT inhibition activity and molecular docking were also investigated.
在这项研究中，将受保护的硼酸酯引入依曲韦林（ETR）的右翼，得到了一系列新型含硼酸酯的衍生物。采用 MTT 法测定了这些新合成的衍生物在 MT-4 细胞中的抗 HIV 效力，并用 ELISA 法测定了它们对 HIV-1 逆转录酶（RT）的抑制活性。大多数合成的化合物对野生型和广泛的 HIV-1 突变株表现出有希望的抗病毒活性。特别是化合物 对野生型和一系列单突变（L100I、K103N、Y181C 和 E138K）表现出最强的活性，EC 值范围为 0.005 至 0.648 μM，优于奈韦拉平（EC = 0.151 μM）。此外，化合物 对双突变株 F227L + V106A 和 RES056 也具有有效的抑制作用，EC 值分别为 3.21 和 2.30 μM。还研究了 RT 抑制活性和分子对接。
