Synthesis and Biological Evaluation of a Series of Quinoline‐Based Quinazolinones and Carbamic Anhydride Derivatives

Abstract

AbstractQuinoline‐based compounds are one of the most important classes of N‐heterocyclics exhibiting a wide spectrum of biological activities. There is a constant demand for the synthesis of new quinoline‐based molecules suitable for therapeutic applications. Here a new strategy is developed to synthesize different quinoline‐based quinazolinones catalytically using InCl3 through a cyclocondensation reaction of isatoic anhydride and aniline with 2‐substituted‐quinoline‐3‐carbaldehyde to produce 2‐(2‐phenoxyquinolin‐3‐yl)‐3‐phenyl‐2,3‐ dihydroquinazolin‐4(1H)‐one derivatives (>90 % yields). In contrast, the reduced electrophilicity at the metal center allows the hydrazide ligand to bind In(III) and serendipitously forms benzoic(2‐phenoxyquinoline‐3‐carbonyl) carbamic anhydride (∼70 % yields). The mechanistic aspects of these reactions were rationally explained. The structure and purity of all the isolated derivatives were assessed by spectroscopic and analytical data. In view of a strong correlation existing between inflammation and cancer progression, the ex‐vivo anti‐inflammatory effect of the ligands was established. The anti‐cancer property of the proposed ligand was delineated with a specific SIRT protein family. Further, the computational docking studies on the binding abilities of 22 synthesized compounds with the Sirt1 protein were discussed in detail.