Identification of potential inhibitory analogs of metastasis tumor antigens (MTAs) using bioactive compounds: revealing therapeutic option to prevent malignancy

• DOI: 10.1007/s11030-021-10345-w
• Publication Date: 2021-11-07T06:02:10Z
• Authors: Anik Banik; Sheikh Rashel Ahmed; Emran Hossain Sajib; Anamika Deb; Shiuly Sinha; Kazi Faizul Azim
• Keywords: 0303 health sciences; Hydrocortisone; Nabumetone; Pemetrexed; Molecular Dynamics Simulation; Ligands; Isoflavones; 3. Good health; Molecular Docking Simulation; 03 medical and health sciences; Antigens, Neoplasm; Neoplasms; Humans; Tramadol

AbstractThe deeper understanding of metastasis phenomenon and detection of drug targets could be a potential approach to minimize cancer mortality. In this study, attempts were taken to unmask novel therapeutics to prevent metastasis and cancer progression. Initially, we explored the physiochemical, structural and functional insights of three metastasis tumor antigens (MTAs) and evaluated some plant based bioactive compounds as potent MTA inhibitors. From 50 plant metabolites screened, isoflavone, gingerol, citronellal and asiatic acid showed maximum binding affinity with all three MTA proteins. The ADME analysis detected no undesirable toxicity that could reduce the drug likeness properties of top plant metabolites. Moreover, molecular dynamics studies revealed that the complexes were stable and showed minimum fluctuation at molecular level. We further performed ligand based virtual screening to identify similar drug molecules using a large collection of 3,76,342 compounds from DrugBank. The results suggested that several structural analogs (e.g. Tramadol, Nabumetone, DGLA, Hydrocortisone) may act as agonist to block the MTA proteins and inhibit cancer progression at early stage. The study could be useful to develop effective medications against cancer metastasis in future. Due to encouraging results, we highly recommend furtherin vitroandin vivotrials for the experimental validation of the findings.