Harnessing Zinc(II) bis-Terpyridine Complex to Overcome Drug Resistance: Mechanistic Insights for Antibacterial Activity

Abstract

The increasing prevalence of drug-resistant bacteria represents a serious global health challenge, prompting scientists to develop innovative antibacterial compounds. An example of such a compound with significant potential as an antibacterial agent is zinc(II) complex ZnL2 of a terpyridine-based ligand 4′-(3,4-diethoxyphenyl)-2,2′:6′,2′′-terpyridine L. The single crystal X-ray diffraction analysis of [ZnL2](ClO4)2.CH3CN.H2O confirms distorted octahedral coordination geometry around zinc(II) in which zinc is coordinated by two terpyridine ligand L. The preliminary investigations identified ZnL2 as a potent antibacterial compound, outperforming widely used antibiotics like amoxicillin, tetracycline, and chloromycin in its action against Bacillus subtilis and Salmonella enterica. The complex ZnL2 efficiently inhibits the development of drug resistance, with 20 passages for B. subtilis and 23 passages for S. enterica, and showed low toxicity towards normal cell lines of Hek 293. As part of the extended investigation, biofilm inhibition, membrane disruption, leakage, and intracellular oxidative stress assays were accompanied. Further analysis of the complex's interactions with DNA was conducted to assess its potential for targeting bacterial DNA as a therapeutic agent. The interaction of the complex with transport proteins such as serum albumin was evaluated to gain an initial understanding of the drug's ADME characteristics. The findings of this study emphasise the substantial antibacterial potential of the newly developed zinc terpyridine complex. Its promising activity could form the basis for future advancement in treatment of bacterial infections.