Insight into the structural requirements of gelatinases (MMP-2 and MMP-9) inhibitors by multiple validated molecular modelling approaches: Part II.

Abstract

Inhibition of the matrix metalloproteinases (MMPs) is effective against metastasis of secondary tumours. Previous MMP inhibitors have failed in clinical trials due to their off-target toxicity in solid tumours. Thus, newer MMP inhibitors now have paramount importance. Here, different molecular modelling techniques were applied on a dataset of 110 gelatinase (MMP-2 and MMP-9) inhibitors. The objectives of the present study were to identify structural fingerprints for gelatinase inhibition and also to develop statistically validated QSAR models for the screening and prediction of different derivatives as MMP-2 (gelatinase A) and MMP-9 (gelatinase B) inhibitors. The Bayesian classification study provided the ROC values for the training set of 0.837 and 0.815 for MMP-2 and MMP-9, respectively. The linear model also produced the leave-one-out cross-validated Q2 of 0.805 (eq. 1, MMP-2) and 0.724 (eq. 2, MMP-9), an r2 of 0.845 (eq. 1, MMP-2) and 0.782 (eq. 2, MMP-9), an r2Pred of 0.806 (eq. 1, MMP-2) and 0.732 (eq. 2, MMP-9). Similarly, non-linear learning models were also statistically significant and reliable. Overall, this study may help in the rational design of newer compounds with higher gelatinase inhibition to fight against both primary and secondary cancers in future.

• Authors: S Das, S A Amin, S Gayen, T Jha
• Journal: SAR and QSAR in environmental research (SAR QSAR Environ Res) Vol. 33 Issue 3 Pg. 167-192 (Mar 2022) ISSN: 1029-046X [Electronic] England
• PMID: 35301933 (Publication Type: Journal Article)

Chemical References

• Gelatinases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Bayes Theorem
• Gelatinases (metabolism)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (chemistry)
• Quantitative Structure-Activity Relationship