Abstract

ctive: Benzothiazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives are the most important pharmacophores and intermediates for making drugs. This study focuses on the preparation and anti-cancer activity of novel benzothiazole-based imidazo[2,1-b][1,3,4]thiadiazole scaffolds. Methods: The synthesized benzothiazolebased imidazo[2,1-b][1,3,4]thiadiazole scaffolds (Va–Vi) were evaluated. The anticancer activity of (Va–Vi) against MCF-7 and A549 cell lines was determined using the MTT assay and screened with in silico molecular docking studies. Results and Discussion: Compounds 2-(6-(4-chlorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)benzo[d]thiazole (Vb), 2-(6-(4-bromophenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)benzo[d]thiazole (Vd), and 2-(6-(4nitrophenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl)benzo[d]thiazole (Vh) exhibited the most potent anticancer activity against MCF-7 and A549 cancer cell lines. Molecular docking studies of all synthesized compounds and erlotinib were also carried out on the EGFR receptor, showing that compounds (Vb), (Vd), and (Vh) had significantly higher binding scores and inhibitory constants than the reference drug erlotinib. Conclusions: It has been observed that the substitution on the 4-chlorophenyl ring (Vb), 4-bromophenyl ring (Vd), and 4-nitrophenyl ring (Vh) is important for maintaining their anticancer activity. The outcomes of the kinase inhibitory assay of these significant (Vb), (Vd), and (Vh) hybrids against the tyrosine kinase EGFR strongly corroborated the in vitro anticancer findings and the in silico docking investigations. The investigation demonstrated that the newly synthesized compounds have the potential as anticancer agents and provided leads for further development.

中文翻译：

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2-(6-苯基咪唑[2,1-b][1,3,4]噻二唑-2-基)苯并[d]噻唑衍生物作为EGFR靶向抗癌药物的合成及生物学评价

摘要

活性：苯并噻唑和咪唑并[2,1- b ][1,3,4]噻二唑衍生物是最重要的药效基团和制备药物的中间体。本研究重点关注新型苯并噻唑基咪唑并[2,1- b ][1,3,4]噻二唑支架的制备及其抗癌活性。方法：对合成的苯并噻唑基咪唑并[2,1- b ][1,3,4]噻二唑支架（Va-Vi）进行评估。 ( Va–Vi ) 针对 MCF-7 和 A549 细胞系的抗癌活性是使用 MTT 测定确定的，并通过计算机分子对接研究进行筛选。结果与讨论：化合物 2-(6-(4-氯苯基)咪唑并[2,1- b ][1,3,4]噻二唑-2-基)苯并[ d ]噻唑 ( Vb )、2-(6- (4-溴苯基)咪唑并[2,1- b ][1,3,4]噻二唑-2-基)苯并[ d ]噻唑( Vd )和2-(6-(4硝基苯基)咪唑[2,1-] b ][1,3,4]噻二唑-2-基)苯并[ d ]噻唑 ( Vh ) 对 MCF-7 和 A549 癌细胞系表现出最有效的抗癌活性。所有合成化合物与厄洛替尼也在EGFR受体上进行了分子对接研究，结果显示化合物( Vb )、( Vd )和( Vh )的结合分数和抑制常数明显高于参比药物厄洛替尼。结论：据观察，4-氯苯环（Vb）、4-溴苯环（Vd）和4-硝基苯环（Vh）上的取代对于维持其抗癌活性很重要。这些针对酪氨酸激酶 EGFR的重要 ( Vb )、( Vd ) 和 ( Vh ) 杂交体的激酶抑制测定结果强烈证实了体外抗癌结果和计算机对接研究。研究表明，新合成的化合物具有作为抗癌药物的潜力，并为进一步开发提供了线索。