Cytotoxicity and Antibacterial Evaluation of O‐Alkylated/Acylated Quinazolin‐4‐one Schiff Bases

Abstract

A series of quinazolin‐4‐one Schiff bases were synthesized and tested in vitro for their cytotoxicity against two cancerous cell lines (MCF‐7, Caco‐2) and a human embryonic cell line (HEK‐293) including their antibacterial evaluation against two Gram‐positive and four Gram‐negative bacterial strains. Most of the quinazoline‐Schiff bases exhibited potent cytotoxicity against Caco‐2. 3‐[(Z)‐({4‐[(But‐2‐yn‐1‐yl)oxy]phenyl}methylidene)amino]‐2‐methylquinazolin‐4(3H)‐one (6f) with the O‐butyne functional group displayed three‐fold higher cytotoxic activity (IC50=376.8 μM) as compared to 5‐fluorouracil (5‐FU; IC50=1086.1 μM). However, all compounds were found to be toxic to HEK‐293, except for 3‐[(Z)‐({4‐[(2,4‐difluorophenyl)methoxy]phenyl}methylidene)amino]‐2‐methylquinazolin‐4(3H)‐one (6h) that showed ∼three‐fold lower toxicity and higher selectivity index than 5‐FU. Structure–activity relationship (SAR) analysis revealed that O‐alkylation generally increased the anticancer activity and selectivity of quinazoline‐4‐one Schiff bases toward Caco‐2 cells. The fluorinated Schiff‐base generally exhibited even more significant cytotoxic activity compared to their chlorine analogs. Surprisingly, none of the quinazoline‐4‐one Schiff bases displayed encouraging antibacterial activity against the bacterial strains investigated. Most of the compounds were predicted to show compliance with the Lipinski parameters and ADMET profiles, indicating their drug‐like properties.

Vegfer-2 Inhibitors and Quinazoline-Based Anticancer Agents

“…All the synthesized compounds (23a-h) were tested in vitro for their cytotoxicity against two cancer cell lines, namely human breast cancer (MCF-7), human colon adenocarcinoma (Caco-2) as well as normal human embryonic cells (HEK-293), using the well-established [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based cell viability assay (Manhas et al 2021).…”

Synthesis, antitumor activity, 3D-QSAR and molecular docking studies of new iodinated 4-(3H)-quinazolinones 3N-substituted

“…These structures are of high interest due to their wide range of biological and pharmacological properties, 1 including antibacterial, 2 antifungal, 3 antitubercular, 4 antimalarial, 5 antitoxoplasma, 6 anti-inflammatory, 7 anti-ulcer, 8 and kinase inhibitor, 9 and anticancer activities. 10 Quinazolines as anticancer agents have received considerable attention since the development of the thymidylate synthetase inhibitors altitrexed and thymitaq. 11 Since then, several quinazolines have been described with anticancer activity, 10 among which the following can be highlighted: inhibitors of epidermal growth factor receptor (EGFR), 12 inhibitors of angiogenesis by inhibiting the vascular endothelial growth factor receptor (VEGFR-2) 13 and dihydrofolate reductase (DHFR) inhibitors that prevent the growth of cancer cells and depletes the cell from thymine causing cell death.…”

“… 10 Quinazolines as anticancer agents have received considerable attention since the development of the thymidylate synthetase inhibitors altitrexed and thymitaq. 11 Since then, several quinazolines have been described with anticancer activity, 10 among which the following can be highlighted: inhibitors of epidermal growth factor receptor (EGFR), 12 inhibitors of angiogenesis by inhibiting the vascular endothelial growth factor receptor (VEGFR-2) 13 and dihydrofolate reductase (DHFR) inhibitors that prevent the growth of cancer cells and depletes the cell from thymine causing cell death. 14 Consequently, DHFR inhibition played an essential role in medicine clinical as antitumor agents and becomes a target for the development of new antitumor agents.…”