Baidya Sandip Kumar, Banerjee Suvankar, Ghosh Balaram, Jha Tarun, Adhikari Nilanjan
Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
Epigenetic Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Shamirpet, Hyderabad, 500078, India.
J Mol Graph Model. 2024 Jan;126:108671. doi: 10.1016/j.jmgm.2023.108671. Epub 2023 Nov 11.
Matrix metalloproteinases (MMPs) are belonging to the Zn-dependent metalloenzymes. These can degenerate the extracellular matrix (ECM) that is entailed with various biological processes. Among the MMP family members, MMP-9 is associated with several pathophysiological circumstances. Apart from wound healing, remodeling of bone, inflammatory mechanisms, and rheumatoid arthritis, MMP-9 has also significant roles in tumor invasion and metastasis. Therefore, MMP-9 has been in the spotlight of anticancer drug discovery programs for more than a decade. In this present study, classification-based QSAR techniques along with fragment-based data mining have been carried out on divergent MMP-9 inhibitors to point out the important structural attributes. This current study may be able to elucidate the importance of several pivotal molecular fragments such as sulfonamide, hydroxamate, i-butyl, and ethoxy functions for imparting potential MMP-9 inhibition. These observations are in correlation with the ligand-bound co-crystal structures of MMP-9. Therefore, these findings are beneficial for the design and discovery of effective MMP-9 inhibitors in the future.
基质金属蛋白酶（MMPs）属于锌依赖性金属酶。这些酶能够降解参与各种生物过程的细胞外基质（ECM）。在MMP家族成员中，MMP-9与多种病理生理情况相关。除了伤口愈合、骨骼重塑、炎症机制和类风湿性关节炎外，MMP-9在肿瘤侵袭和转移中也具有重要作用。因此，十多年来，MMP-9一直是抗癌药物研发项目的焦点。在本研究中，对不同的MMP-9抑制剂进行了基于分类的定量构效关系（QSAR）技术以及基于片段的数据挖掘，以指出重要的结构属性。当前的这项研究或许能够阐明一些关键分子片段如磺酰胺、异羟肟酸、异丁基和乙氧基官能团对于赋予潜在MMP-9抑制作用的重要性。这些观察结果与MMP-9的配体结合共晶体结构相关。因此，这些发现对于未来有效MMP-9抑制剂的设计和发现是有益的。
