Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Synthesis and molecular docking of new hydrazones derived from ethyl isonipecotate and their biological activities

A Munir¹, Aziz-ur-Rehman ¹ , M A Abbasi¹, S Z Siddiqui¹, A Nasir², S G Khan, S Rasool¹, S AA Shah¹

¹Department of Chemistry, Government College University, Lahore-54000; ²Human Molecular Genetic Lab (HMG), Faculty of Biological Science, Department of Biochemistry Quaid-I-Azam University Islamabad; ³Department of Chemistry, Government College University, Faisalabad, Pakistan; ⁴Faculty of Pharmacy, Universiti Teknologi Mara, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia; ⁵Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Universiti Teknologi Mara, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.

For correspondence:- Aziz-ur-Rehman Email: rehman@gcu.edu.pk Tel:+9242111000010

Received: 17 November 2016 Accepted: 16 April 2017 Published: 30 May 2017

Citation: Munir A, A, Abbasi MA, Siddiqui SZ, Nasir A, Khan SG, et al. Synthesis and molecular docking of new hydrazones derived from ethyl isonipecotate and their biological activities. Trop J Pharm Res 2017; 16(5):1157-1165 doi: 10.4314/tjpr.v16i5.25

© 2017 The authors.
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Abstract

Purpose: To investigate the antibacterial and α-glucosidase inhibitory activities of hydrazone derivatives (8a-h) of ethyl isonipecotate.

Methods: The reaction of ethyl isonipecotate (2) with 3,5-dichloro-2-hydroxybenzenesulfonyl chloride (1) in an aqueous basic medium yielded ethyl 1-[(3,5-dichloro-2-hydroxyphenyl)sulfonyl]piperidin-4-carboxylate (3). Compound 3 was subsequently converted to ethyl 1-[(3,5-dichloro-2-ethoxyphenyl)sulfonyl]piperidin-4-carboxylate (5) via O-alkylation. Compound 5 on reaction with hydrated hydrazine yielded 1-[(3,5-dichloro-2-ethoxyphenyl)sulfonyl]piperidin-4-carbohyrazide (6) in MeOH. Target compounds 8a-h were synthesized by stirring 6 with different aromatic aldehydes (7a-h) in MeOH. All the synthesized compounds were structurally elucidated by proton nuclear magnetic resonance (¹H-NMR), electron impact mass spectrometry (EI-MS) and infrared (IR) spectroscopy. For antibacterial activity, solutions of the synthesized compounds were mixed with bacterial strains, and the change in absorbance before and after incubation was determined. For enzyme inhibitory activity, change in the absorbance of mixtures of synthesized compounds and enzyme before and after incubation with substrate was determined.

Results: The target compounds were synthesized in appreciable yields and well characterized by spectral data analysis. Salmonella typhi was inhibited by 8e (MIC 8.00 ± 0.54 µM), Escherichia coli by 8f (8.21 ± 0.83 µM), Bacillus subtilis by 8c (8.56 ± 0.63 µM) and Staphylococcus aureus by 8c (8.86 ± 0.29 µM). Two compounds, 8e and 8d, were very effective inhibitors of α-glucosidase with IC₅₀ values of 40.62 ± 0.07 and 48.64 ± 0.08 µM, respectively.

Conclusion: Low IC₅₀ values of the synthesized compounds against α-glucosidase demonstrates their potential in type-2 diabetes treatment. Furthermore, these compounds exhibit substantial antibacterial activity against the bacterial strains tested

Keywords: Antibacterial activity, ^5;-Glucosidase inhibition, Ethyl isonipecotate, Hydrazones