In vitro and in silico screening reveals low-cytotoxicity topoisomerase I inhibitors in plant and coral fungi extracts, highlighting viable leads for safer antitumor drugs.
Key Points
Identify novel, low-cytotoxicity DNA topoisomerase I (Topo I) inhibitors from natural product sources to address the clinical toxicity challenges of current antitumor agents.
Screened a library of 138 low-cytotoxic or non-cytotoxic compounds sourced from coral-associated fungi and plants.
Conducted molecular docking simulations paired with in vitro bioassays to assess topoisomerase I inhibition.
Identified eight potent Topo I inhibitors capable of inhibiting enzyme-mediated relaxation of supercoiled DNA at concentrations ranging from 5 to 100 µM.
Flavonoids exhibited greater Topo I inhibitory activity compared to other evaluated compound classes.