2-Mercaptobenzimidazole Derivatives as Novel Butyrylcholinesterase Inhibitors: Biology-Oriented Drug Synthesis (BIODS), In-Vitro and In-Silico Evaluation | [Journal of Chemical Society of Pakistan • 2020]

Author(s):

1. Muhammad Yousaf: Department of Chemistry, Abdul Wali Khan University,Mardan- 23200,Pakistan

2. Faima Alam: Department of Biochemistry, Abdul Wali Khan University,Mardan- 23200, Pakistan

3. Abdul Sadiq: Department of Pharmacy, University of Malakand, P.O. Box 18800, Dir Lower, Khyber Pakhtunkhwa, Pakistan.

4. Muhammad Saeed Jan: Department of Pharmacy, University of Malakand, P.O. Box 18800, Dir Lower, Khyber Pakhtunkhwa, Pakistan.

5. Ashfaq Ur Rehman: Department of Biochemistry, Abdul Wali Khan University, Mardan- 23200, Pakistan

6. Abdul Wadood: Department of Biochemistry, Abdul Wali Khan University,Mardan- 23200, Pakistan

7. Mumtaz Ali: 2Department of Chemistry, University of Malakand, P.O. Box 18800, Dir Lower Khyber Pakhtunkhwa, Pakistan.

8. Momin Khan: Department of Chemistry, University of Malakand,P.O. Box 18800, Dir Lower Khyber Pakhtunkhwa, Pakistan

Abstract:

Summary: Schiff bases gaining remarkable importance day by day in the current situation Schiff bases are found to be a valuable pharmacophore for the synthesis and development of various biologically active heterocyclic compounds. In recent past, we have reported various classes of compounds as enzyme inhibitors, in continuation; A series of 2-Mercaptobenzimidazole hydrazone derivatives (9-42) were synthesized through multistep reactions in high yields and evaluated for butyrylcholinesterase inhibition. In present study, 2-ethylthio benzimidazole was formed by the reaction of 2Mercaptobenzimidazole with bromoethane. In the second step (2-(2-(ethylthio)benzimidazolyl)acetate) obtained by the reaction of 2-ethylthio benzimidazole with ethyl chloroacetate. In the third step, 2-(2(ethylthio)benzimidazolyl)acetate was refluxed in methanol with hydrazine hydrate and get 2((ethylthio)benzimidazolyl)acetohyrazide. In the last step, 2-((ethylthio)benzimidazolyl)acetohyrazide was reacted with different aldehydes in the presence of glacial acetic acid (catalyst) to get a series of 2Mercaptobenzimidazole hydrazone derivatives. Product was characterized by 1H NMR and 13C NMR. These newly synthesized compounds showed varying degree of butyrylcholinesterase inhibition. Compound no. 15 with (IC50 = 25.10 ± 0.90 µM) was found to be most active in the whole series. Similarly, compounds 42, 12, 40, 17, 22, 28 and 09 exhibited excellent activity with IC50 values are (IC50 = 25.36 ± 0.57 µM, IC50 = 27.30 ± 0.52 µM, IC50 = 34.31 ± 0.59 µM, IC50 = 51.29 ± 0.64 µM, IC50 = 54.52 ± 0.95 µM, IC50 = 57.90 ± 0.45 µM and IC50 = 60.93 ±0.67 µM) respectively as compared to standard galantamine 18.13±0.20 µM. Molecular docking helped to find interactions between butyrylcholinesterase enzyme and test compounds. This study results that Schiff bases have been discovered a new class of butyrylcholinesterase inhibitors which have not been discovered earlier.

Page(s): 263-273

DOI: DOI not available

Published: Journal: Journal of Chemical Society of Pakistan, Volume: 42, Issue: 2, Year: 2020

Keywords:

In silico , Hydrazone Schiffs bases , Benzimidazole2thiol

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