吡罗昔康类似物的设计、合成、对接研究及作为有前途的抗 HIV-1 药物的生物学评价。
Piroxicam Analogs: Design, Synthesis, Docking Study and Biological Evaluation as Promising Anti-HIV-1 Agents.
机构信息
Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hepatitis and AIDS department, Pasteur institute of Iran, Tehran, Iran.
出版信息
Med Chem. 2022;18(2):209-219. doi: 10.2174/1573406417666210125141639.
OBJECTIVE
In this study, we describe the synthesis, docking study and biological evaluation of 1,2-benzothiazines 1,1-dioxide derivatives.
METHODS
Taking the well-known drug, Piroxicam as a lead compound, we designed and synthesized two series of 1,2-benzothiazines 1,1-dioxide derivatives to assay their ability in inhibition of HIV-1 replication in cell culture.
RESULTS
Most of the new compounds were active in the cell-based anti-HIV-1 assay with EC50 < 50 μM. Among them, compound 7g was found to be the most active molecule.Docking study using 3OYA pdb code on the most active molecule 7g with EC50 values of 10 μM showed a similar binding mode to the HIV integrase inhibitors.
CONCLUSION
Since all the compounds showed no remarkable cytotoxicity (CC50> 500 μM), the designed scaffold is promising structure for the development of new anti-HIV-1 agents.
目的
在这项研究中，我们描述了 1,2-苯并噻嗪 1,1-二氧化物衍生物的合成、对接研究和生物学评价。
方法
以著名药物吡罗昔康为先导化合物，我们设计并合成了两个系列的 1,2-苯并噻嗪 1,1-二氧化物衍生物，以检测它们在细胞培养中抑制 HIV-1 复制的能力。
结果
大多数新化合物在基于细胞的抗 HIV-1 测定中具有 EC50<50μM 的活性。其中，化合物 7g 被发现是最活跃的分子。用 3OYA pdb 代码对 EC50 值为 10μM 的最活跃分子 7g 进行对接研究表明，其结合模式与 HIV 整合酶抑制剂相似。
结论
由于所有化合物均无明显细胞毒性（CC50>500μM），因此设计的支架有望成为开发新型抗 HIV-1 药物的结构。
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