New quinazoline sulfonamide derivatives as potential anticancer agents: Identifying a promising hit with dual EGFR/VEGFR-2 inhibitory and radiosensitizing activity.

Autor: Ghorab MM; Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo 11787, Egypt. Electronic address: mmsghorab@yahoo.com., Soliman AM; Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo 11787, Egypt. Electronic address: Aiten_mahmoud@yahoo.com., El-Adl K; Pharmaceutical Medicinal Chemistry and Drug Design Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Heliopolis University for Sustainable Development, Cairo, Egypt., Hanafy NS; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Heliopolis University for Sustainable Development, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2023 Nov; Vol. 140, pp. 106791. Date of Electronic Publication: 2023 Aug 15.
DOI: 10.1016/j.bioorg.2023.106791
Abstrakt: 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 EGFR T790M 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 EGFR T790M and VEGFR-2. Compound 15 showed the most significant cytotoxic activity with IC 50  = 0.0977 µM against MCF-7 and the most potent inhibitory activity against both EGFR and VEGFR with IC 50  = 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE