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Bioactive Fluorenes. Part II. Unprecedented biologically active thiazole derivatives based-2,7-dichlorofluorene as competent DHFR inhibitors: Design, synthesis, and molecular docking approaches
Arabian Journal of Chemistry ( IF 6 ) Pub Date : 2020-05-01 , DOI: 10.1016/j.arabjc.2020.03.024
Reem I. Alsantali , Essam M. Hussein , Rami J. Obaid , Moataz Morad , Hatem M. Altass , Ahmed Alharbi , Ahmed M. Hameed , Rabab.S. Jassas , Mohamed A.S. Abourehab , Basim H. Asghar , Ziad Moussa , Saleh A. Ahmed

Abstract In this study, a new series of (4-(2,7-dichloro-9H-fluoren-4-yl)thiazol-yl)acetamide derivatives was synthesized, and the new heterocycles were completely characterized, evaluated for their antimicrobial activity, and screened for cytotoxic activity against human lung carcinoma (A-549) and human breast carcinoma (MCF-7) cell lines. A molecular docking study was undertaken to identify the possible mode of action of the synthesized compounds, which suggested binding interactions with the dihydrofolate reductase (DHFR) active sites. Most of the synthesized compounds displayed meaningful activity against A-549 and MCF-7 cell lines when compared to 5-fluorouracil (5-FU), which was used as a reference drug. Furthermore, some of the prepared compounds exhibited potent antibacterial and antifungal activities. The highly pronounced biological activities of the compounds under investigation offer such species as promising future drug prospects which may find applications in the fields of biological and medicinal sciences.

中文翻译:

生物活性芴。第二部分。前所未有的生物活性噻唑衍生物基于 2,7-二氯芴作为有效的 DHFR 抑制剂:设计、合成和分子对接方法

摘要 本研究合成了一系列新的(4-(2,7-二氯-9H-芴-4-基)噻唑-基)乙酰胺衍生物,并对新的杂环化合物进行了完整的表征,评价了它们的抗菌活性,并筛选了对人肺癌 (A-549) 和人乳腺癌 (MCF-7) 细胞系的细胞毒活性。进行了分子对接研究以确定合成化合物的可能作用模式,这表明与二氢叶酸还原酶 (DHFR) 活性位点的结合相互作用。与用作参考药物的 5-氟尿嘧啶 (5-FU) 相比,大多数合成的化合物对 A-549 和 MCF-7 细胞系显示出有意义的活性。此外,一些制备的化合物表现出有效的抗菌和抗真菌活性。
更新日期:2020-05-01
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