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3-取代 5,5-二苯基咪唑烷-2,4-二酮衍生物的合成、分子对接、ADMET 评价及对 RD 和 L20B 细胞系的细胞毒性活性评价。

Synthesis, molecular docking, ADMET evaluation and cytotoxic activity evaluation on RD and L20B cell lines of 3-substituted 5,5-diphenylimidazolidine-2,4-dione derivatives.

机构信息

Laboratory of Medicinal Chemistry, Drug Sciences Research Center, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Morocco.

Biotechnology Laboratory, Faculty of Medicine and Pharmacy, Mohammed V University, Morocco.

出版信息

J Biomol Struct Dyn. 2023 Jul;41(10):4592-4600. doi: 10.1080/07391102.2022.2069865. Epub 2022 May 1.

DOI:10.1080/07391102.2022.2069865
PMID:35491728
Abstract

Hydantoins comprise an important class of compounds which have long attracted attention due to their remarkable biological and pharmacological properties including antitumor and antiviral activities. As a continuation of our studies on hydantoins derivatives we report the successful synthesis of hydantoins derivatives. These synthesized compounds were evaluated for their cytotoxic activity against (African green monkey kidney cell line) and Human cell lines using methotrexate drug () as a reference drug in cytotoxic activity studies. The percentage of the cell line viability was carried out by using Trypan blue dye exclusion method. The tested compounds showed equipotent cytotoxicity effect against (L20B) and a moderate effect against Human () cell lines. These results exhibited better activity for 4a-b compounds than the reference drug methotrexate (MTX). Molecular docking studies indicated that the synthesized compounds are suitable inhibitors of humain dihydrofolate reductase (DHFR) enzyme, which may explain the high antiproliferative activity.Communicated by Ramaswamy H. Sarma.

摘要

海因衍生物是一类重要的化合物,由于其显著的生物学和药理学特性,包括抗肿瘤和抗病毒活性,长期以来一直引起人们的关注。作为我们对海因衍生物研究的继续,我们成功地合成了海因衍生物。这些合成的化合物被评估了它们对非洲绿猴肾细胞系(L20B)和人细胞系的细胞毒性活性,以甲氨蝶呤药物(MTX)作为细胞毒性活性研究中的参考药物。通过使用台盼蓝染料排除法进行细胞系存活率的百分比测定。测试的化合物对 L20B 细胞系表现出等效的细胞毒性作用,对人细胞系()表现出中等活性。这些结果表明 4a-b 化合物比参考药物甲氨蝶呤(MTX)具有更好的活性。分子对接研究表明,合成的化合物是人类二氢叶酸还原酶(DHFR)酶的合适抑制剂,这可能解释了高抗增殖活性。由 Ramaswamy H. Sarma 传达。

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