Antimicrobial efficacy of cyanobacterium Synechococcus pevalekii extracts against MDR bacteria and fungi; an integrated GC-MS, molecular docking and MD simulation study.

This study evaluates the antimicrobial properties of marine unicellular cyanobacterium Synechococcus pevalekii using integrated in vitro and in silico approach. Solvents including methanol, ethanol, ethyl acetate, butanol and acetone were used for biomass extraction and were assessed against a collection of pathogens, such as Staphylococcus aureus, Streptococcus pyogenes, Klebsiella pneumoniae, Escherichia coli, Candida tropicalis, and Trichophyton rubrum. The butanol and ethyl acetate extracts emerged as the most potent; the butanol extract exhibited a maximum ZOI of 22 mm against E. coli, while the ethyl acetate extract reached 20 mm against K. pneumoniae. Both extracts had low MIC of 1.56 mg/mL. In terms of antioxidant activity, the methanol extract was the most active with IC50 of 1.48 ± 0.02 μg /mL, and the ethyl acetate extract was the least active with IC50 of 1.91 ± 0.03 μg/mL. The GC-MS analysis identified a number of major bioactive metabolites. Computational validation of six of these compounds was done using molecular docking and 100-ns molecular dynamics (MD) simulations against three target receptors (PDB IDs: 1AJ0, 1AD1, and 1J71). 2,3-Dihydro-5-nitro-1H-indazol-3-one (CID: 5,374,661) typically had the highest binding affinity to receptor 1J71 with a docking score of - 6.924 kcal/moL, and the stability of the R3L1 complex was ensured with a low protein RMSD (2.2 A) and 2-3 active hydrogen bonds during the entire trajectory. These results suggest that S. pevalekii is a potent source of antimicrobial agents, with 2,3-Dihydro-5-nitro-1H-indazol-3-one identified as a promising biochemical scaffold for further therapeutic development.