Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Synthesis of some new propanamide derivatives bearing 4-piperidinyl-1,3,4-oxadiazole, and their evaluation as promising anticancer agents

Aziz-ur-Rehman ¹ , N Ahtzaz¹, M A Abbasi¹, S Z Siddiqui¹, S Saleem¹, S Manzoor¹, J Iqbal¹, N A Virk¹, T A Chohan², S AA Shah³

¹Department of Chemistry, Government College University; ²Faculty of Pharmacy, University of Central Punjab, 1-Khayaban-e-Jinnah Road Johar Town, Lahore-54000, Pakistan; ³Faculty of Pharmacy and Atta-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

Accepted: 15 May 2018 Published: 30 June 2018

Citation: A, Ahtzaz N, Abbasi MA, Siddiqui SZ, Saleem S, Manzoor S, et al. Synthesis of some new propanamide derivatives bearing 4-piperidinyl-1,3,4-oxadiazole, and their evaluation as promising anticancer agents. Trop J Pharm Res 2018; 17(6):1145-1153 doi: 10.4314/tjpr.v17i6.22

© 2018 The authors.
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Abstract

Purpose: To sequentially synthesize piperidine-4-carboxylic acid ethyl ester-appended 1,3,4-oxadiazole hybrids and to evaluate them as anticancer agents.

Methods: Ethyl 1-[(4-methylphenyl)sulfonyl]-4-piperidinecarboxylate (1) was synthesized from 4-methylbenzenesulfonylchloride (a) and ethyl 4-piperidinecarboxylate (b). Compound (1) was converted into ethyl 1-[(4-methylphenyl)sulfonyl]-4-piperidine carbohydrazides (2) and 5-{1-[(4-methylphenyl)sulfonyl]-4-piperidinyl}-1,3,4-oxadiazole-2-thiol (3) respectively. A variety of aryl amine (4a-l) were treated with 2-bromopropionylbromide to synthesize an array of propanamide (5a-l). Finally, 5-{1-[(4-methylphenyl)sulfonyl]-4-piperidinyl}-1,3,4-oxadiazole-2-thiol (3) and propanamides (5a-l) were reacted to synthesize target compounds (6a-l). Purity compounds 6a-l was confirmed by spectroscopic techniques like (¹H-NMR), (¹³C-NMR) and EI-MS. To determine their anticancer potential, the change in absorbance of mixture and cell line before and after incubation was determined.

Results: All the compounds 6a-l were successfully synthesized in 73-85 % yield. Compounds 6h, 6j and 6e have low IC₅₀ (±SD) values of 20.12 ± 6.20, 10.84 ± 4.2 and 24.57 ± 1.62 µM to act as strong anticancer agents relative to doxorubicin (0.92 ± 0.1 µM) used as a reference.

Conclusion: The synthesized propanamide derivatives bearing 4-piperidinyl-1,3,4-oxadiazole are potential anticancer agents, but further studies, especially in vivo, are required to ascertain their therapeutic usefulness.

Keywords: Ethyl isonipecotate, Propanamides, 1,3,4-Oxadiazole, Anti-cancer activity