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• W4285404518 abstract "Quinazoline scaffold has shown excellent antitumor activity and has aroused public attention because of its low toxicity, high efficiency and unique mode of action. In this paper, five quinazoline analogs D1-D5 were preliminary designed through scaffold shopping from mTOR inhibitors and synthesized in four steps. Five compounds exhibited potent antitumor activity against the HepG2 cell line by MTT assay. Compound D2 (IC50 = 4.06 µM) was found as the most potent analog and showed better antiproliferative ability than sorafenib (IC50 = 6.14 µM). The result of the wound healing assay and transwell migration assay indicated D2 strong potential to suppress HepG2 cell migration in a dose- and time-dependent manner. The underlying mechanism of its cytotoxicity was also investigated and the results of western blotting confirmed that D2 exposure could block the cell cycle, promote apoptosis and inhibit AKT and mTOR phosphorylation in HepG2 cells. Molecular docking further supported that D2 showed a high affinity to mTOR kinase. The results favored our rational design intention and hinted the new quinazolines might be helpful in the further explorations of potent agents." @default.
• W4285404518 created "2022-07-14" @default.
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• W4285404518 date "2022-11-01" @default.
• W4285404518 modified "2023-10-06" @default.
• W4285404518 title "Design, synthesis and antitumor evaluation of novel quinazoline analogs in hepatocellular carcinoma cell" @default.
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• W4285404518 doi "https://doi.org/10.1016/j.molstruc.2022.133718" @default.
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