Structural analysis of arylsulfonamide-based carboxylic acid derivatives: a QSAR study to identify the structural contri
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ORIGINAL RESEARCH
Structural analysis of arylsulfonamide-based carboxylic acid derivatives: a QSAR study to identify the structural contributors toward their MMP-9 inhibition Subha Mondal 1 & Suvankar Banerjee 1 & Sk. Abdul Amin 1 & Tarun Jha 1 Received: 11 August 2020 / Accepted: 7 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Matrix metalloproteinases (MMPs) are a group of endopeptidases renowned for their ability to degrade the extracellular matrix (ECM) and contribute in different physiological processes. Matrix metalloproteinase 9 (MMP-9) is a member of this zincdependent family of peptidases which also contributes to several pathophysiological disorders including a wide variety of cancer and tumor conditions besides the normal physiological processes. Thus, the development of MMP-9 inhibitors has always been an important target for combating the disorders related to it. Meanwhile, the aryl sulfonamide moiety is one of the structural attributes which can be found frequently in many MMP-9 inhibitors. Additionally, the carboxylic acid group is an interesting zinc-binding group (ZBG) which is able to deliver good chelation with the catalytic zinc of the metalloproteinases. In this study, different molecular modeling approaches were undertaken for a set of diverse MMP-9 inhibitors, containing an arylsulfonamide moiety and a carboxylic acid group in order to identify the structural features contributing toward their activity variation. From this study, the importance of structural features including tetrazole, biphenyl, and carboxamide moieties as well as fundamental molecular properties like molecular weight, number of rings, and hydrogen bond acceptors for their MMP-9 inhibition was observed which will be helpful for further development the MMP-9 inhibitors. Keywords Matrix metalloproteinase . MMP-9 inhibitor . MLR . Non-linear QSAR . Bayesian model . Recursive partitioning . Decision tree
Introduction Matrix metalloproteinases (MMPs), a group of zincdependent endopeptidases, possess the capability to regulate, degrade, and remodel the extracellular matrix (ECM) component which are essential for physiological as well as biological activities in the human body [1–3]. MMPs also have diverse roles and functions in various diseases including Subha Mondal and Suvankar Banerjee contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11224-020-01635-4) contains supplementary material, which is available to authorized users. * Tarun Jha [email protected] 1
Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, P. O. Box 17020, Kolkata 700032, India
cardiovascular diseases, neurodegenerative diseases, rheumatoid arthritis, periodontitis, and cancers [4]. Normally, MMPs are expressed at a low level and controlled by tissue inhibitor of matrix metalloproteinases (TIMPs). The overexpression of MMPs can cause an imba
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