Design, Synthesis and Biological Evaluation of 7‐Substituted‐1,3‐diaminopyrrol[3,2‐f]quinazolines as Potential Antibacterial Agents

Abstract

AbstractThe evolution of drug‐resistant bacteria poses a serious threat to public health; hence, it is imperative to develop new and efficient antibiotics. Irresistin‐16 (IRS‐16) is a dual‐target antibacterial candidate that affects folate biosynthesis and membrane integrity and exhibits potent lethality against various bacteria. In this study, a series of 1,3‐diamino‐7H‐pyrrol[3,2‐f]quinazoline (DAPQ) derivatives based on IRS‐16 was designed and synthesized to identify outstanding antibacterial candidates. The most promising compound, 7‐(4‐(4‐methylpiperazin‐1‐yl) benzyl)‐7H‐pyrrol[3,2‐f] quinazoline‐1,3‐diamine (18 e), displayed excellent antibacterial activity against both gram‐positive and gram‐negative bacteria (minimum inhibitory concentrations=1–4 μg/mL), improved water solubility, poor hemolytic activity and low cytotoxicity. Compound 18 e exhibited rapid bactericidal properties and prevented bacterial resistance in laboratory simulations. These results provide a basis for the development of new DAPQ‐based compounds to combat emerging bacterial resistance.