Inhibitory potential of Malabaricone C and Quercetagetin against aberrantly expressed Maternal Embryonic Leucine...

Annually, Hepatocellular Carcinoma promotes 905,677 fresh occurrences and causes about 830,180 mortalities globally. The fatal predominant neoplasia is one of the most aggressive and multi-factorial form of primary liver cancer. The yearly escalated sum of occurrences and fatalities are reported due to poor diagnostic system leading to late-stage diagnosis of tumors and inept treatment consequences. Henceforth, the present analysis aims to identify nascent HCC-associated biomarkers and their respective plant-derived small molecule inhibitors. In this place, meta-analysis of seven (GSE101685, GSE112790, GSE84402, GSE62232, GSE45436, GSE33006 and GSE6222) micro-array profiles including an aggregate of 443 HCC-tumor and normal liver samples has been implemented through GeneSpring software. The resultant 433 DEGs including 117 up-regulated genes and 316 down-regulated genes were subjected to functional annotation, pathway enrichment and gene-disease association analysis through Enrichr webserver. Sequentially, the top 10 hub nodes were recognized by employing Cytoscape software and MELK being the most frequently interacting node was reflected as the anti-HCC target. Eventually, the Molecular docking, Molecular dynamic simulations and MMGBSA analysis were accomplished by Schrödinger software for the plausible anti-HCC MELK target against plant-derived small molecules retrieved from NPASS database. The outcomes indicated potential phytocompounds Malabaricone C and Quercetagetin with steady interactions and enhanced binding affinities for MELK target. Thus, the study conclusively postulates plant-derived small molecules Malabaricone C and Quercetagetin as promising MELK inhibitors for targeting HCC patients with elated MELK expression levels. Conversely, the study fabricates a computational groundwork for MELK-associated targeted HCC therapeutics and simultaneously also sustains the obligatory molecular validations of the phytochemicals for clinical drug-development applications.

The online version contains supplementary material available at 10.1007/s40203-025-00463-w.