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

• Published in: Tropical Journal of Pharmaceutical Research
• Main Author: Aziz-Ur-Rehman; Ahtzaz N.; Abbasi M.A.; Siddiqui S.Z.; Saleem S.; Manzoor S.; Iqbal J.; Virk N.A.; Chohan T.A.; Shah S.A.A.
• Format: Article
• Language: English
• Published: University of Benin 2018
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85049457291&doi=10.4314%2ftjpr.v17i6.22&partnerID=40&md5=759d1d61e518baf55c66c92221487500

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 (1 H-NMR), (13 C-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. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria and 2018 The authors.