Exploring the Potential of Plant Cytokinins Against Common Human Pathogens: In Vitro Assessment and In Silico Insights

Cytokinins, plant hormones derived from adenine, are best known for regulating growth and stress responses in plants. Recent findings suggest they may also influence microbial viability, yet their direct antimicrobial potential remains underexplored. This study evaluates the antimicrobial activities of four natural cytokinins (iPA, B, K, and p-T) and their N9-ribosides (iPAR, BR, KR, and p-TR) against selected human pathogens. Using the broth microdilution method, we assessed their effects on Gram-positive and Gram-negative bacteria, as well as fungal strains. While Gram-negative species showed no susceptibility, all tested compounds exhibited bacteriostatic activity against Bacillus subtilis and Enterococcus faecalis. Most notably, kinetin (K) and kinetin riboside (KR) displayed strong antifungal activity against Candida albicans, with MIC values comparable to the reference drug nystatin. Molecular docking studies supported these findings by showing that K and KR form favorable interactions with two validated antifungal targets in Candida albicans: secreted aspartic proteinase 3 (SAP3) and dihydrofolate reductase (DHFR). This is, to our knowledge, the first report linking natural cytokinins to direct antifungal action against C. albicans supported by in silico evidence. These findings highlight the potential of K and KR as promising leads for the development of cytokinin-based antifungal agents.