Computational discovery of plant-based inhibitors against human carbonic anhydrase IX and molecular dynamics simulation

Carbonic anhydrase IX (hCAIX) is a membrane-spanning metalloenzyme, encoded by CA9 gene, which can lead to various carcinomas if upregulated. Due to its overexpression in many cancer tissues, hCAIX has become a promising target for developing anticancer therapeutics. Furthermore, several classes of small-molecules have shown to inhibit the hCAIX expression. In this study, therefore, we screened (n = 42) plant-derived compounds to identify the most potent hCAIX inhibitors and to understand their interactions with hCAIX and drug candidacy through in silico approaches. Among all, only three compounds (i.e. fraxoside, scopolin, and xanthone,) provided higher binding affinity toward hCAIX protein as compared to the native ligand. In standard docking, scopolin showed −4.97 kcal/mol of binding energy with hCAIX while control ligand…