Modified Hummel-Dreyer Method and Molecular Modeling Studies Identified Nicotinic Acid Analogues as Carbonic Anhydrase III Ligands

Author(s): Nada Jarrar, Muhammed Alzweiri, Yusuf Al-Hiari, Shrouq Farah, Mohammad A. Khanfar

Journal Name: Letters in Drug Design & Discovery

Volume 13 , Issue 5 , 2016

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Graphical Abstract:


The anti-hyperlipidemic effect of nicotinic acid and its ability to overexpress PPARγ combined with the recently elucidated role of carbonic anhydrase III (CAIII) in of PPARγ expression, suggested the possibility that nicotinic acid inhibits CAIII. To validate this hypothesis we docked nicotinic acid into the binding pocket of CAIII. Apparently, nicotinic acid shared at least four critical binding interactions with potent CAIII inhibitor. Subsequent experimental validation using Hummel– Dreyer method indicated that nicotinic acid indeed inhibited the enzymatic activity of CAIII with an Ki value of 203 µM. Additional eighteen nicotinic acid analogues were tested and seven compounds were more active than nicotinic acid with ki values ranging 69.7- 115.2 µM. Docking studies and QSAR analysis were applied to explore the structural requirements for inhibiting CAIII and to build self-consistent and predictive model. Our findings strongly suggest that CAIII inhibition is at least one of the mechanisms for the reported anti-hyperlipidemic properties of nicotinic acid.

Keywords: Nicotinic acid, QSAR, docking, carbonic anhydrase, hummel–dreyer.

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Article Details

Year: 2016
Published on: 14 April, 2016
Page: [401 - 410]
Pages: 10
DOI: 10.2174/1570180812666150821002900
Price: $65

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