Biochemical Basis of the Antimicrobial Activity of Quinazolinone Derivatives in the Light of Insights Into the Features of the Chemical Structure and Ways of Binding to Target Molecules. A Review

Abstract

The review characterizes the role of the main targets of antibacterial agents: “efflux pumps”; enzymes (DNA-hyruases as a subclass of topoisomerases, homoserine transacetylase, various classes of sorbitases, aromatics, lipoteichoyl synthase, polyketide synthase, pantothenate synthetase, acetyl-CoA carboxylase, sensory histidine kinase, kinase, cyclooxygenase, etc.); penicillin-binding protein; quorum signaling and adhesin systems in important biochemical processes of pathogen maintenance and virulence manifestation. The possibility of manifestation of antimicrobial effect by the substance upon its binding to the protein molecules responsible for pathogenicity of a microorganism was shown. The role of quinazolinone derivatives exhibiting high reactivity, stability in chemical processes and characterized by a wide spectrum of pharmacological activity including antimicrobial activity with respect to various gram-positive and gram-negative bacteria was determined. It has been shown that changes in the compound structure through the introduction of different substituents modify the degree of hydrophilicity and, as a result, determine a different degree of drug penetration through the cell membrane; the ability to form intermediate complex compounds stabilized by hydrogen bonds and van der Waals and stacking interactions with enzymatic targets as well as receptor-regulator proteins and signaling systems of pathogen cells. The results on prediction of the mechanism of action of the compounds synthesized by the authors of the article by methods of mathematical modeling are presented. The possibility of creating combined structures based on the quinazolinone core with various heterocyclic derivatives as a product with a pronounced antimicrobial activity is assessed. The considered regularities are of practical importance for the specialists in the field of medicinal chemistry, organic synthesis, biotechnology, clinical pharmacology, pharmaceutical chemistry and technology whose efforts are aimed at obtaining a new drug substance.