Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Synthesis and cytotoxicity studies on new pyrazole-containing oxime ester derivatives

Arzu Karakurt¹ , İrem Bozbey¹, Harun Uslu¹, Suat Sari², Zeynep Özdemir¹, Emine Salva³

¹Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Inonu University, 44280, Malatya, Turkey; ²Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100, Ankara, Turkey; ³Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Inonu University, 44280, Malatya, Turkey.

For correspondence:- Arzu Karakurt Email: arzukarakurt@hotmail.com Tel:+904223410660

Accepted: 14 May 2019 Published: 30 June 2019

Citation: Karakurt A, Bozbey &, Uslu H, Sari S, Özdemir Z, Salva E. Synthesis and cytotoxicity studies on new pyrazole-containing oxime ester derivatives. Trop J Pharm Res 2019; 18(6):1315-1322 doi: 10.4314/tjpr.v18i6.24

© 2019 The authors.
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Abstract

Purpose: To synthesize a series of new 1-(2-naphthyl)-2-(1H-pyrazol-1-yl)ethanone oxime ester derivatives (5-12) with potential anticancer properties, and to determine their cytotoxic effects in mouse fibroblast and human neuroblastoma cell lines.

Methods: The title compounds were obtained through sodium salt reaction of 1-(naphthalene-2-yl)-2-(1H-pyrazol-1-yl)etanone oxime (4) with various acyl chlorides. The cytotoxic effects were evaluated by MTS colorimetric assay, while physicochemical descriptors were calculated using QikProp software.

Results: Most of the compounds showed approximately 50 – 60 % inhibition against SH-SY5Y neuroblastoma cells at 100 μM. Of these, compound 7a was the most active combination with an IC₅₀ value of 85.94 µM. The toxic effect of the compounds on mouse fibroblast cell line was insignificant (p < 0.05) even when the dose was increased. The calculated physicochemical properties of the compounds were within drug-like chemical space.

Conclusion: The synthesized oxime ester derivatives with pyrazole ring exhibit selective toxicity to neuroblastoma cells without affecting healthy mouse fibroblast cells. The compounds proved to be drug-like while their pharmacokinetic features were also encouraging, and were in line with in silico predictions.

Keywords: Cytotoxic activity, E/Z isomer, Neuroblastoma cell, Oxime ester, Pyrazole