Synthesis of Novel Benzimidazole Analogs for Neurodegenerative Diseases by Targeting Prolyl Oligopeptidase

Author:

Shakoor Abdul1,Alam Aftab2ORCID,Ali Mumtaz2,Ullah Saeed3,Halim Sobia Ahsan3,Rehman Munir Ur4,AlAsmari Abdullah F.5,Alasmari Fawaz5,Khan Ajmal3ORCID,Khan Momin1,Al‐Harrasi Ahmed3

Affiliation:

1. Department of Chemistry Abdul Wali Khan University Mardan 23200 Pakistan

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

3. Natural and Medical Sciences Research Center University of Nizwa, PO Box 33 616 Birkat Al Mauz, Nizwa Oman

4. Heilongjiang Provincial Key Laboratory of CO2 Resource Utilization and Energy Catalytic Materials School of Material Science and Chemical Engineering Harbin University of Science and Technology No. 4, Linyuan Road Harbin 150040 People's Republic of China

5. Department of Pharmacology and Toxicology College of Pharmacy King Saud University Riyadh 11451 Saudi Arabia

Abstract

AbstractA novel series of benzimidazole hydrazone‐Schiff bases have been prepared through multi‐step reaction process and structurally confirmed by13C‐,1H‐NMR and HR‐MS (ESI) spectroscopic techniques and evaluated against prolyl oligopeptidase (POP) inhibitory activity. In the series, eleven derivatives 20, 14 15, 19, 10, 9, 11, 4, 5, 18, and 21 revealed excellent inhibition potential having IC50 values from (IC50=1.44±0.08 μM) to (IC50=5.66±0.48 μM). However, six out of twenty compounds 12, 16, 13, 17, 22, and 3 attributed significant activity while, three compounds were found good active in the range of IC50 values 10.43±0.57 to 11.45±0.63 μM. The docking studies indicates that the hydrazone moiety show an imperative part in binding with one of the catalytic residues (Arg643) in the substrate binding region of POP enzyme. The excellent inhibitions of these compounds for POP enzyme may lead them to be a good candidates for drug against neurodegenerative diseases.

Publisher

Wiley

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