New 5-cyano-6-oxo-pyridine-based sulfonamides (6a–m and 8a–d) were designed and synthesized to potentially inhibit both the epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA), with anticancer properties. First, the in vitro anticancer activity of each target substance was tested using Henrietta Lacks cancer cell line and M.D. anderson metastasis breast cancer cell line cells. Then, the possible CA inhibition against the human CA isoforms I, II, and IX was investigated, together with the EGFR inhibitory activity, with the most powerful derivatives. The neighboring methoxy group may have had a steric effect on the target sulfonamides, which prevented them from effectively inhibiting the CA isoforms while effectively inhibiting the EGFR. The effects of the 5-cyanopyridine derivatives 6e and 6l on cell-cycle disruption and the apoptotic potential were then investigated. To investigate the binding mechanism and stability of the target molecules, thorough molecular modeling assessments, including docking and dynamic simulation, were performed.

中文翻译：

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鉴定 3-(5-氰基-6-氧代-吡啶-2-基)苯磺酰胺作为具有 EGFR 抑制活性的新型抗癌药物

设计和合成了新型 5-氰基-6-氧代-吡啶基磺酰胺（6a-m和8a-d），可潜在抑制表皮生长因子受体 (EGFR) 和碳酸酐酶 (CA)，并具有抗癌特性。首先，使用Henrietta Lacks癌细胞系和MD anderson转移乳腺癌细胞系细胞测试了每种目标物质的体外抗癌活性。然后，使用最强大的衍生物研究了 CA 对人 CA 亚型 I、II 和 IX 的可能抑制作用，以及 EGFR 抑制活性。邻近的甲氧基可能对目标磺胺类药物具有空间效应，从而阻止它们在有效抑制 EGFR 的同时有效抑制 CA 同工型。然后研究了5-氰基吡啶衍生物6e和6l对细胞周期破坏和细胞凋亡潜力的影响。为了研究目标分子的结合机制和稳定性，进行了彻底的分子建模评估，包括对接和动态模拟。