Design, molecular docking, synthesis, characterization, biological activity evaluation (against MES model), in-silico biological activity spectrum (PASS analysis), toxicological and predicted oral rat LD₅₀ studies of novel sulphonamide derivatives

Abstract

BACKGROUND: Among the reported potential agents to treat the epilepsy, sulphonamides are important and their significance cannot be ignored. A series of substituted 4-amino-benzene sulfonamides were designed, keeping in view the structural requirement of pharmacophore.

METHODS: Lipinski rule of five has been calculated; failure to Lipinski rule was not observed. Docking was performed through AutoDock Vina. Molecules have been screened out through docking. Compounds were synthesized and characterized through IR, ¹HNMR, ¹³C NMR, Mass and elemental analysis. The anticonvulsant activity of the synthesized compounds was assessed using the Maximal Electroshock Seizure (MES) model. In-silico biological activity spectrum, toxicological studies, predicted oral rats LD50 were performed.

RESULTS: Docking studies showed good interaction with lyase (Oxo-acid) - human carbonic anhydrase-I (1AZM). The in-silico studies proved them to be with good drug-likeness properties, especially 4-(3-Acetyl-phenylamino)-methyl)-benzenesulfonamide (2g). These results revealed that the synthesized compounds (1a-1c, 2a-2q) exhibited promising anticonvulsant effect against MES model for inhibition of Lyase- Human Carbonic Anhydrase-I.

CONCLUSION: After investigating all the results, the compound 4-(3-Acetyl-phenylamino)-methyl)-benzenesulfonamide (2g) is found to be best in the series. A comparatively good activity of compound 2g suggests us that sulphonamide can be leads to further optimization for building potent and chemically diversified anti-convulsant agents.

Keywords

anticonvulsant / sulfonamide / docking / in-silico studies

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Acknowledgment

One of the authors (Ajeet) is thankful to Ms. Pratibha Priti Maurya, Owner, CBBE, India for in-silico studies, and thankful to Dr. Om Prakash, Post Doctorate Fellow, University of Lucknow, India for interpretation and support of In-silico studies.

Author’s contribution

Ajeet conceptualized overall study design and carried synthesis, biological studies, analyzed and interpreted data. Dr. Arvind Kumar and Dr. Arun Kumar Mishra analyzed and revised the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Permission was sought from Institutional Animal Ethics Committee, IFTM University, India for carrying biological studies (Animal studies) under Registration No. 837/ac/04/CPCSEA and Resolution No. 2015/837ac/PhD/04.

Conflicts of interest

None conflict of interest declared.

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