Design, synthesis, characterization, enzymatic inhibition evaluations, and docking study of novel quinazolinone derivatives

Abstract

In this study, novel quinazolinone derivatives 7a-n were synthesized and evaluated against metabolic enzymes including α-glycosidase, acetylcholinesterase, butyrylcholinesterase, human carbonic anhydrase I, and II. These compounds exhibited high inhibitory activities in comparison to used standard inhibitors with K_i values in the range of 19.28-135.88 nM for α-glycosidase (K_i value for standard inhibitor = 187.71 nM), 0.68-23.01 nM for acetylcholinesterase (K_i value for standard inhibitor = 53.31 nM), 1.01-29.56 nM for butyrylcholinesterase (K_i value for standard inhibitor = 58.16 nM), 10.25-126.05 nM for human carbonic anhydrase I (K_i value for standard inhibitor = 248.18 nM), and 13.46-178.35 nM for human carbonic anhydrase II (K_i value for standard inhibitor = 323.72). Furthermore, the most potent compounds against each enzyme were selected in order to evaluate interaction modes of these compounds in the active site of the target enzyme. Cytotoxicity assay of the title compounds 7a-n against cancer cell lines MCF-7 and LNCaP demonstrated that these compounds do not show significant cytotoxic effects.

Keywords: Cytotoxicity; Enzyme inhibition; Metronidazole; Molecular docking; Quinazolinone.