ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Synthesis and antimicrobial evaluation of novel naringenin-based isopropanolamine hybrid derivatives

Tian-Tian Chen, Meng Xiang, Zhang-Min Xiang, and Hua Cao

School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan, People’s Republic of China

E-mail: xiangzm@live.com

Received: 7 August 2025  Accepted: 7 December 2025

Abstract:

In order to discover novel antibacterial agents, a series of 19 novel isopropanolamine hybrid derivatives based on the natural flavonoid naringenin were synthesized via a concise two-step route and evaluated for their antibacterial activities against five bacterial strains, including Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), and Salmonella paratyphi B (S. paratyphi B). Bioassay results demonstrated that several hybrid compounds exhibited significantly improved antibacterial activity against Gram-positive bacteria, including S. aureus and B. subtilis compared to the parent compound naringenin (MIC = 512 and 256 μg/mL, respectively). Notably, compounds A₆ and A₇ displayed the most potent activity, with MIC values of 32 μg/mL against both S. aureus and B. subtilis. To further investigate antibacterial efficacy, bacterial growth curve assays were conducted, revealing that compounds delayed bacterial proliferation in a dose-dependent manner. Scanning electron microscopy analysis showed concentration-dependent morphological damage, including membrane shrinkage, pore formation, and cell disruption. These findings suggest that the antibacterial activity of the synthesized compounds may involve disruption of the bacterial cytoplasmic membrane, interference with protein function, and alteration of cell morphology and physiological integrity. This study provides a promising strategy for the development of natural product-based antibacterial agents.

Keywords: Naringenin derivatives; Isopropanolamine; Antimicrobial activity; Mode of action; Synthesis

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-025-04582-8

Chemical Papers 80 (5) 4721–4737 (2026)