Abstract

In the present work, a series of bisbenzazole derivatives were designed and synthesized as antiproliferative agents. The antiproliferative activity of these compounds was investigated using MTT assay. Bisbenzazole derivatives showed significant antiproliferative activity against all the four tested cancer cell lines. Among the various bisbenzazole derivatives, bisbenzoxazole derivatives exhibited the most promising anticancer activity followed by bisbenzimidazole and bisbenzothiazole derivatives. All the derivatives were found to be less toxic as compared to methotrexate (positive control) in normal human cells, indicating selective and efficient antiproliferative activity of these bisbenzazole derivatives. The structure–activity relationships of heteroaromatic systems and linkers present in bisbenzazole derivatives were analyzed in detail. In silico ADMET prediction revealed that bisbenzazole is a drug-like small molecule with a favorable safety profile. Compound 31 is a potential antiproliferative hit compound that exhibits unique cytotoxic activity distinct from methotrexate.

Graphic abstract

Twenty-one bisbenzoxazole derivatives have been designed synthesized and evaluated to be an antiproliferative activity against four human tumor cell lines.

中文翻译：

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头对头双苯并唑衍生物作为抗增殖剂：设计、合成、体外活性和 SAR 分析。

摘要

在目前的工作中，设计并合成了一系列双苯并唑衍生物作为抗增殖剂。使用 MTT 法研究这些化合物的抗增殖活性。双苯并唑衍生物对所有四种测试的癌细胞系均显示出显着的抗增殖活性。在各种双苯并唑衍生物中，双苯并恶唑衍生物表现出最有希望的抗癌活性，其次是双苯并咪唑和双苯并噻唑衍生物。与甲氨蝶呤（阳性对照）相比，所有衍生物在正常人细胞中的毒性较低，表明这些双苯并唑衍生物具有选择性和有效的抗增殖活性。详细分析了双苯并唑衍生物中存在的杂芳族系统和接头的构效关系。计算机 ADMET 预测显示，双苯并唑是一种药物样小分子，具有良好的安全性。化合物31是一种潜在的抗增殖打击化合物，具有不同于甲氨蝶呤的独特细胞毒活性。

图形摘要

已设计合成了 21 种双苯并恶唑衍生物，并对其进行了评估，这些衍生物对四种人类肿瘤细胞系具有抗增殖活性。