Antimicrobial and Antiproliferative Activities and Enzyme Binding Affinity of Xanthen-3-one Derivatives

Abstract

Ten biologically active derivatives of 2,6,7-trihydroxyxanthen-3-one, previously synthesized and characterised, were investigated for their in vitro antimicrobial and antiproliferative activity. Compounds were tested on three bacteria, Staphylococcus aureus, Bacillus subtilis and Escherichia coli, and two fungi strains, Candida albicans, and Saccharomyces cerevisiae. The best activity against E. coli showed non-substituted compound 1. The most potent against fungi strains was compound 7 with ortho methoxy substituent. Compound 4 exerted the most potent antiproliferative activity in the micromolar range (0.1–10 µM) on tested tumour cell lines except on SW620. Additional Western blot analyses showed increased cyclin B1 levels in HeLa cells treated with compound 4, which is a major mitotic catastrophe’s marker and decreased levels of Wee1 and Erk ½ kinases involved in regulation of the mitotic process. The most potent compounds after in vitro tests were subjected to molecular docking simulations to evaluate enzyme binding affinity, and provide further evidence for experimentally observed biological effects in vitro.

Keywords

• xanthenes
• antibacterial and antifungal activity
• induction of cell death
• enzyme binding modes
• docking study
• bioavailability prediction