No abstract

A series of novel quinazolinone hydrazide derivatives were designed and synthesized as EGFR inhibitors. The results indicated that most of the aimed compounds had potential anti‐tumor cell proliferation and EGFR inhibitory activities. In the comprehensive analysis of all the tested compounds, the target compound 9c showed the best anti‐tumor cell proliferation activity, (IC50=1.31 μM for MCF‐7, IC50=1.89 μM for HepG2, IC50=2.10 μM for SGC), and IC50=0.59 μM for the EGFR inhibitory activity. Docking results showed that compound 9c could ideally insert the active site and interact with the critical amino acid residues (Val702, Lys721, Met769, Asp831) in the active site.

Fatty acid biosynthesis is essential for bacterial survival. Of these promising targets, β‐ketoacyl‐acyl carrier protein (ACP) synthase III (FabH) is the most attractive target. A series of novel 1,3,4‐oxadiazole‐2(3H)‐thione derivatives containing 1,4‐benzodioxane skeleton targeting FabH were designed and synthesized. These compounds were determined by 1H‐NMR, 13C‐NMR, MS and further confirmed by crystallographic diffraction study for compound 7m and 7n. Most of the compounds exhibited good inhibitory activity against bacteria by computer‐assisted screening, antibacterial activity test and E. coli FabH inhibitory activity test, wherein compounds 7e and 7q exhibited the most significant inhibitory activities. Besides, compound 7q showed the best E. coli FabH inhibitory activity (IC50=2.45 μΜ). Computational docking studies also showed that compound 7q interacts with FabH critical residues in the active site.