Lavendustin C 是一种源自天然产物的抗癌先导化合物，通过酯化或酰胺化对其羧基进行修饰（化合物 6-10），并通过引入 5-亚芳基噻唑啉-4-酮对其氨基进行修饰（14a-c 至 17a-c） 、18a 和 18b)。使用两种策略来组合这些部分并优化产量。评估了这些新化合物对九种癌细胞系的抗增殖活性。结果清楚地表明 5-arylidenethiazolin-4-one 部分对该活性有很大贡献。此外，甲酯比酰胺更有效，而 N-乙基酰胺是酰胺中最有效的。 14b 显示针对所有测试的癌细胞系的最高效力，IC50 为 1.4-2.5 µM，而针对正常细胞系的 IC50 > 50 µM。结果显示 HeLa 细胞停滞在 G0/G1、S 期，G2/M 期细胞百分比减少。此外，14b 通过诱导细胞凋亡引发 HeLa 癌细胞死亡。发现 14b 的 EGFR 抑制效力与厄洛替尼相当。进行并讨论了计算对接和计算机药代动力学研究。总之，14b 可以作为进一步开发抗癌药物的多靶点先导化合物。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Lavendustin C, a natural-product derived anticancer lead compound, was modified at its carboxylic group by esterification or amidation (compounds 6-10) and at its amino group by introducing 5-arylidenethiazolin-4-ones (14a-c to 17a-c, 18a and 18b). Two strategies were used to combine these moieties and to optimize the yield. These new compounds were evaluated for their antiproliferative activities against a panel of nine cancer cell lines. The results clearly show that 5-arylidenethiazolin-4-one moiety contributes substantially to the activity. Also, methyl esters are more potent than amides, while N-ethylamides are the most potent among amides. 14b showed the highest potency against all tested cancer cell lines with IC50 1.4-2.5 µM, while against normal cell line IC50 > 50 µM. It showed arrest of HeLa cells at G0/G1, S phases and reduction of the percent of cells in G2/M. Moreover, 14b triggered death of HeLa cancer cells via apoptosis induction. EGFR inhibitory potency of 14b was found to be comparable to that of erlotinib. Computational docking and in silico pharmacokinetic studies were performed and discussed. In conclusion, 14b might serve as a multitarget lead compound for further development of anticancer agents.Copyright © 2024 Elsevier Inc. All rights reserved.