Exploration of structural alerts and fingerprints for novel anticancer therapeutics: a robust classification-QSAR dependent structural analysis of drug-like MMP-9 inhibitors.

Among various matrix metalloproteinases (MMPs), overexpression of MMP9 has been established as a key player in a variety of cancers. Therefore, MMP9 has emerged as a promising biomolecule that may be targeted to design potent inhibitors as novel anticancer therapeutics. In this study, a large database containing 1,123 drug-like MMP-9 inhibitors was considered for robust classification-dependent fragment-based QSAR study through SARpy, Bayesian classification, and recursive partitioning analyses and were validated by both internal and external validation techniques. In a nutshell, all these classification-dependent techniques revealed some common structural alerts and sub-structural fingerprints responsible for modulating MMP-9 inhibition. These observations are in agreement with the interactions obtained from the ligand-bound co-crystal structures of MMP-9 justifying the robustness of the current study. Finally, based on these crucial structural fragments, some new lead compounds were designed and further validated by the binding mode of interaction analysis. Therefore, these findings may be beneficial in designing novel and potential MMP-9 inhibitors in the future as a weapon to combat several cancers.