取代苯并咪唑共轭 1,3,4-恶二唑的设计、合成及细胞毒性评价。

Design, Synthesis and Cytotoxicity Evalufation of Substituted Benzimidazole Conjugated 1,3,4-Oxadiazoles.

机构信息

Department of Chemistry, College of Natural Sciences, Can Tho University.

Institute of Natural Medicine, University of Toyama.

出版信息

Chem Pharm Bull (Tokyo). 2022;70(6):448-453. doi: 10.1248/cpb.c22-00162.

DOI:10.1248/cpb.c22-00162

PMID:35650042

Abstract

Two series of 2-substituted benzimidazole conjugated 1,3,4-oxadiazole derivatives were designed, synthesized and evaluated for their cytotoxic activities against the three human cancer cell lines (cervical cancer (HeLa), breast cancer (MCF-7) and lung cancer (A549)). As the results 14 compounds demonstrated consistent to stronger cytotoxicities compared to the control 5-fluorouracil (5-FU) towards the tested cell lines including 4c (HeLa); 4b, 4e, 4h, 7i-j, 7m-n, 7s (MCF-7); 7b (MCF-7, A549); 7h (HeLa, MCF-7); and 4d, 4i, 7c (HeLa, MCF-7, A549), with the IC ranging from 2.7 to 38 µM. Notably, compound 4b illustrated almost 5-fold activity against the MCF-7 while 4d, 4i were 9- and 8-fold (HeLa), 4.5- and 13-fold (MCF-7), 4.7- and 4-fold (A549) increase in activity compared to 5-FU, respectively, and were found as lead compounds. These findings suggest that compounds 4b, 4d and 4i merit further characterization and can serve as promising scaffolds in the discovery of new potent anticancer agents.

摘要

设计、合成了两个系列的 2-取代苯并咪唑共轭 1,3,4-噁二唑衍生物，并评价了它们对三种人癌细胞系（宫颈癌（HeLa）、乳腺癌（MCF-7）和肺癌（A549））的细胞毒性活性。结果表明，与对照 5-氟尿嘧啶（5-FU）相比，14 种化合物对测试的细胞系表现出一致的或更强的细胞毒性，包括 4c（HeLa）；4b、4e、4h、7i-j、7m-n、7s（MCF-7）；7b（MCF-7、A549）；7h（HeLa、MCF-7）；4d、4i、7c（HeLa、MCF-7、A549），IC50 值范围为 2.7 至 38 μM。值得注意的是，化合物 4b 对 MCF-7 的活性几乎提高了 5 倍，而 4d、4i 对 HeLa 的活性分别提高了 9 倍和 8 倍，对 MCF-7 的活性分别提高了 4.5 倍和 13 倍，对 A549 的活性分别提高了 4.7 倍和 4 倍，与 5-FU 相比，4b、4d 和 4i 被认为是先导化合物。这些发现表明，化合物 4b、4d 和 4i 值得进一步研究，并可作为发现新的有效抗癌药物的有前途的支架。