A Rational Approach towards the Development of Human Carbonic Anhydrase Inhibitors as Antiepileptic Agent
- *Corresponding Author:
- Kalyan K Sethi
Department of Pharmaceutical Science and Technology
Birla Institute of Technology, Mesra, Ranchi-835 215, Jharkhand, India
E-mail: [email protected]
Received date: May 04, 2016; Accepted date: June 14, 2016; Published date: June 20, 2016
Citation: Sethi KK, Nayak PK, Sarkar H, Verma SM (2016) A Rational Approach towards the Development of Human Carbonic Anhydrase Inhibitors as Antiepileptic Agent. Med chem (Los Angeles) 6:405-410. doi:10.4172/2161-0444.1000377
Copyright: © 2016 Sethi KK, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Antiepileptic activity study considering the MES model and molecular docking studies were performed for a series of previously synthesized dioxoisoindolin benzene sulfonamide derivatives. The reported molecules were investigated as inhibitors of the zinc metalloenzyme carbonic anhydrase (CA, EC 220.127.116.11), specifically against the hCA I and II isoforms. To get a better insight of these molecules as potential inhibitors we specifically consider the hCA I (Ki values in the range 159 nM to >10000 nM) and hCAII (Ki values in range 1.7 nM to >10000 nM). The most potential molecule explored in the study was 3-(4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl)benzenesulfonamide (Ki=27.7 nM), 3-chloro-4-(4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl)benzenesulfonamide(Ki=4.9 nM) and 4-((4-nitro-1,3-dioxoisoindolin-2-yl)methyl)benzenesulfonamide (Ki=34 nM) respectively with obtained p-value <0.01 in the MES study and showed higher antepileptic activity than acetazolamide (AZM). Moreover a well defined docking score with RMSD value of 1.8 throws light on their effective binding to the active site of both 1AZM and 1ZFQ respectively.