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