Molecular docking study of coumarin-hydroxybenzohydrazide hybrid as an inhibitor of carbonic anhydrases IX and XII

M. Antonijević, Dušica M Simijonović, D. Milenkovic, Z. Marković
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Abstract

Carbonic anhydrase isoforms IX and XII are crucial for the regulation of extracellular pH thus facilitating cancer cell proliferation, invasion, and metastasis. Therefore, discovering good inhibitors of CA-IX and CA-XII is of great importance. In this study, the inhibitory activity of previously synthesized coumarin-hydroxybenzohydrazide 3a and its parent molecule 4-hydroxycoumarin, against enzymes CA-IX and CA-XII was investigated. For that purpose, the molecular docking study was performed. The activity of both investigated compounds was calculated for neutral and anionic species. The obtained results indicate that compound 3a expresses good inhibitory activity towards both investigated enzymes, but inhibitory activity is significantly better towards CA-XII than CA-IX.
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香豆素-羟基苯并肼杂化物作为碳酸酐酶IX和XII抑制剂的分子对接研究
碳酸酐酶异构体IX和XII对调节细胞外pH至关重要,从而促进癌细胞的增殖、侵袭和转移。因此,寻找CA-IX和CA-XII的良好抑制剂具有重要意义。本研究考察了先前合成的香豆素-羟基苯并肼3a及其母体分子4-羟基香豆素对CA-IX和CA-XII酶的抑制活性。为此,进行了分子对接研究。计算了两种化合物的中性和阴离子活性。结果表明,化合物3a对两种酶均表现出良好的抑制活性,但对CA-XII的抑制活性明显优于CA-IX。
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