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

ABSTRACT

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.

KEYWORDS:

• Arylsulfonamide
• MMP-2
• molecular docking-based QSAR
• CoMFA
• CoMSIA
• molecular dynamics simulation

Acknowledgements

SB is thankful to the Swami Vivekananda Merit-cum-Means (SVMCM) scholarship, Govt. of West Bengal, India, for awarding the scholarship. BG is thankful to the Department of Health Research, India (File No. 11013_33_2021-GIA HR), Govt. of India and Council of Scientific and Industrial Research (CSIR-37(1722)/19/EMR-II), Govt. of India, for providing research grants. NA is thankful to the authority of Jadavpur University for providing the research grant to conduct the research work. The authors are sincerely thankful to the Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India, and the Department of Pharmacy, BITS-Pilani, Hyderabad Campus, India, for providing the necessary research facilities.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary data

Supplemental data for this article can be accessed at: https://doi.org/10.1080/1062936X.2023.2261842.

Additional information

Funding

The work was supported by the Council of Scientific and Industrial Research, India [CSIR-37(1722)/19/EMR-II]; Swami Vivekananda Merit-cum-Means (SVMCM) scholarship, Govt. of West Bengal, India [WBP201610602311].