Investigation of the inhibitory effects of isoindoline-1,3-dion derivatives on hCA-I and hCA-II enzyme activities
| Autor: | Hayrunnisa Nadaroglu, Özlem Gündoğdu, Nurhan Kishali, Mehlika Dilek Altıntop, Belgin Sever, Azize Alayli Gungor |
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| Přispěvatelé: | Anadolu Üniversitesi, Eczacılık Fakültesi, Farmasötik Kimya Anabilim Dalı, Sever, Belgin, Altıntop, Mehlika Dilek, Kırşehir Ahi Evran Üniversitesi, Kaman Meslek Yüksekokulu, Gıda İşleme Bölümü |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
chemistry.chemical_classification
biology 010405 organic chemistry Stereochemistry Organic Chemistry Isoindoline 010402 general chemistry 01 natural sciences Isozyme 0104 chemical sciences Analytical Chemistry Molecular Docking Inorganic Chemistry Carbonic Anhydrase chemistry.chemical_compound Enzyme chemistry Affinity chromatography Carbonic anhydrase biology.protein Salt bridge Isoindoline-1 3-Diones IC50 Spectroscopy ADME |
| Popis: | Inhibition of carbonic anhydrase (CA) has emerged as a promising approach for the treatment of a variety of diseases such as glaucoma, epilepsy, obesity and cancer. As a result, the design of CA inhibitors (CAIs) is an outstanding field of medicinal chemistry. Due to the therapeutic potential of isoindoline-1,3-diones as CAIs, herein hCA I and hCA II isozymes were purified from human erythrocytes using affinity chromatography and the inhibitory effects of a series of isoindoline-1,3-diones on hydratase activities of these isozymes were investigated. Among these compounds, compound 3a was found to be the most effective compound on hCA I with an IC50 value of 7.02 µM, whereas compound 3c was the most potent compound on hCA II with an IC50 value of 6.39 µM. Moreover, molecular docking studies were carried out for all compounds and acetazolamide (AAZ), the reference agent, in the active sites of hCA I and hCA II. Generally, the compounds showed high affinity through salt bridge formation and metal coordination with Zn2+ ion and ?-stacking interaction with His94 residue. According to in silico Absorption, Distribution, Metabolism and Excretion (ADME) studies, the pharmacokinetic parameters of all compounds were within the acceptable range All studies related to the kinetics and inhibition studies of hCA I and hCA II enzyme in this study was financially supported by a the project numbered FAD-2018-6321 from Research Development Center of Ataturk University, Turkey . Appendix A |
| Databáze: | OpenAIRE |
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