Unravelling structurally diverse broad-spectrum antimicrobial secondary metabolites isolated from the stem of Tinospora cordifolia.

Abstract

Antimicrobial resistance (AMR) is one of the most critical global health challenges of the 21st century; there is an urgent need to discover and develop novel antimicrobial agents to strengthen the current therapeutic armamentarium. Subsequently, natural products serve as a reservoir of unique and structurally diverse molecules, which offer promising opportunities for discovering and developing novel therapeutics to combat AMR. In our present study, phytochemical investigation of the stems of Tinospora cordifolia, an Ayurvedic medicinal plant, resulted in the isolation of 28 chemical constituents. Their structures were elucidated by comprehensive spectroscopic analyses, including 1D, 2D NMR, and HRESI-MS. All isolated compounds were then screened for antibacterial potential against a panel of clinically relevant Gram-positive (Staphylococcus aureus) and Gram-negative (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli) pathogens. Initial screening at 25 μM concentration revealed three active hits (TC-1, TC-2, and TC-6), which were further evaluated by MIC and MBC determination assays. All three compounds exhibited MIC and MBC values in the range of 0.015 μM to 16 μM and 0.015 μM to 32 μM, respectively. Furthermore, cytotoxicity assessment using murine macrophages (RAW 264.7 and J774A.1) revealed good biocompatibility with a satisfactory selectivity index, while hemolysis assays confirmed very minimal erythrocyte toxicity at the tested concentration. Furthermore, in silico ADME/toxicity analysis using SwissADME and pkCSM predicted favourable pharmacokinetics and drug-likeness properties, although structural optimization may further improve their developability. Collectively, these findings underscore the potential of TC-1, TC-2, and TC-6 as valuable candidates for novel antibacterial drug development.