Related Experiment Video
Updated: Jun 26, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Design, synthesis, and antibacterial activity study of pyrroloquinazoline diamine derivatives
Muchun Cheng1, YaJing Tian1, JieYa Shang1
1Affiliated Hospital of Jinggangshan University, Jiangxi Province Key Laboratory of Organ Development and Epigenetics, College of Traditional Chinese Medicine and Pharmacy, Jinggangshan University, Ji'an, Jiangxi, P.R. China.
Abstract:
To combat antimicrobial resistance (AMR), a novel series of pyrrolo[3,2-f]quinazoline-diamine (PQD) derivatives (5a-5z) featuring a flexible benzyl-oxo-benzyl side chain were designed and synthesised via structural optimisation of lead compound IRS-16. All compounds exhibited potent dihydrofolate reductase (DHFR) inhibition. Compound 5a was most notable, showing exceptional enzymatic inhibition (IC50 = 0.92 nM), surpassing both IRS-16 and trimethoprim. 5a demonstrated broad-spectrum antibacterial activity against Gram-positive (e.g., E. faecalis) and Gram-negative strains (e.g., E. coli), as well as clinical isolates of S. aureus, K. pneumoniae, and uropathogenic E. coli (UPEC), with MIC values as low as 0.5 μg/mL. It displayed rapid bactericidal action, low resistance propensity, and inhibited biofilm formation by >90% at 0.5 μg/mL. Additional mechanisms included disruption of bacterial membrane integrity, causing leakage of cellular contents. These results identify 5a as a promising lead for developing novel, broad-spectrum DHFR inhibitors with a low resistance risk.
Related Concept Videos
Aryldiazonium Salts to Azo Dyes: Diazo Coupling
Inhibitors of Bacterial DNA Synthesis
Gene Regulation in Microbial Communities: Quorum Sensing
Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence its...
Diazonium Group Substitution: –OH and –H

