Assessing structural insights into in-house arylsulfonyl L-(+) glutamine MMP-2 inhibitors as promising anticancer agents through structure-based computational modelling approaches

• Published in: SAR and QSAR in environmental research Vol. 34; no. 10; pp. 805 - 830
• Main Authors: Baidya, S.K., Banerjee, S., Ghosh, B., Jha, T., Adhikari, N.
• Format: Journal Article
• Language: English
• Published: Abingdon Taylor & Francis 03.10.2023; Taylor & Francis Ltd
• Subjects: Amino acids; Anticancer properties; Antitumor agents; Arylsulfonamide; Cancer; CoMFA; Computer applications; CoMSIA; Docking; Drug development; Gelatinase A; Glutamine; Hydrogen bonding; Hydrogen bonds; Hydrophobicity; Inhibitors; Leukemia; MMP-2; molecular docking-based QSAR; molecular dynamics simulation; Progressions; Structure-activity relationships
• ISSN: 1062-936X; 1029-046X; 1029-046X
• DOI: 10.1080/1062936X.2023.2261842

MMP-2 is potentially contributing to several cancer progressions including leukaemias. Therefore, considering MMP-2 as a promising target, novel anticancer compounds may be designed. Here, 32 in-house arylsulfonyl L-(+) glutamines were subjected to various structure-based computational modelling approaches to recognize crucial structural attributes along with the spatial orientation for higher MMP-2 inhibition. Again, the docking-based 2D-QSAR study revealed that the Coulomb energy conferred by Tyr142 and total interaction energy conferred by Ala84 was crucial for MMP-2 inhibition. Importantly, the docking-dependent CoMFA and CoMSIA study revealed the importance of favourable steric, electrostatic, and hydrophobic substituents at the terminal phenyl ring. The MD simulation study revealed a lower fluctuation in the RMSD, RMSF, and Rg values indicating stable binding interactions of MMP-2 and these molecules. Moreover, the residual hydrogen bond and their interaction analysis disclosed crucial amino acid residues responsible for forming potential hydrogen bonding for higher MMP-2 inhibition. The results can effectively aid in the design and discovery of promising small-molecule drug-like MMP-2 inhibitors with greater anticancer potential in the future.