本文报告了一系列新的喹唑啉磺胺偶联物2-16的合成以及它们作为EGFRT790M和VEGFR-2双重靶点的潜在抗癌剂的评估。新合成的化合物基于目标受体的结构要求进行设计，并通过光谱数据进行了确认。利用MTT试验评估了这些化合物对四种癌细胞系（HepG2、MCF-7、HCT116和A549）的细胞毒性。最活性的化合物进一步评估了它们对EGFRT790M和VEGFR-2的抑制活性。化合物15显示出对MCF-7的最显著的细胞毒性活性，IC50 = 0.0977 µM，并对EGFR和VEGFR都显示出最强的抑制活性，IC50分别为0.0728和0.0523 µM。化合物15能够诱导MCF-7细胞的凋亡，并在G2/M期阻滞细胞周期。使用HEK-293正常细胞系评估了化合物15的相对安全性，并进行了ADMET评估。化合物15的放射敏化评估证明了其对癌细胞在单剂量为8 Gy的γ射线照射后敏化的显著能力。分子对接研究揭示了化合物15能够与EGF和VEGF受体的ATP结合位点结合，从而抑制它们的活性。版权所有 © 2023 Elsevier Inc. 保留所有权利。

Herein, we report the synthesis of a series of new quinazoline sulfonamide conjugates 2-16 and their evaluation as potential anticancer agents via dual targeting of EGFRT790M and VEGFR-2. The newly synthesized compounds were designed based on the structure requirements of the target receptors and were confirmed using spectral data. The compounds were evaluated for their cytotoxicity against four cancer cell lines (HepG2, MCF-7, HCT116 and A549) using MTT assay. The most active compounds were further evaluated for their inhibitory activity against EGFRT790M and VEGFR-2. Compound 15 showed the most significant cytotoxic activity with IC50 = 0.0977 µM against MCF-7 and the most potent inhibitory activity against both EGFR and VEGFR with IC50 = 0.0728 and 0.0523 µM, respectively. Compound 15 was able to induce apoptosis in MCF-7 cells and cell cycle arrest at the G2/M phase. The relative safety profile of 15 was assessed using HEK-293 normal cell line and an ADMET profile was carried out. Radiosensitizing evaluation of 15 proved its significant ability to sensitize the cancer cell to the effect of radiation after being subjected to a single dose of 8 Gy gamma irradiation. Molecular docking studies revealed that 15 could bind to the ATP-binding site of EGF and VEGF receptors, inhibiting their activity.Copyright © 2023 Elsevier Inc. All rights reserved.