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

The 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.