Design, Synthesis and Biological Screening of Novel 1,5-Diphenyl-3-(4-(trifluoromethyl)phenyl)-2-pyrazoline Derivatives

Fatih Tok,Bedia Koçyiğit-Kaymakçıoğlu

doi:10.17344/acsi.2020.6028

Abstract

1-Phenyl-5-substituted-3-(4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-pyrazole derivatives were synthesized from chalcone derivatives. The structures of compounds were characterized by IR, 1H NMR spectroscopic methods and elemental analysis. All compounds were evaluated for their in vitro antioxidant activity using DPPH and ABTS methods, anti-inflammatory activity using lipoxygenase inhibitory method and antidiabetic activity using the ?-glucosidase inhibitory method. Especially, pyrazoline derivatives exhibited stronger anti-inflammatory activity than the reference drug indomethacin (IC50: 50.45 µM) and their IC50 values were in the range of 0.68 and 4.45 µM. In addition, the ADME properties of all chalcone and pyrazoline derivatives were calculated by Lipinski's and Veber's rules.

Highlights

Pyrazoline scaffolds bearing five-membered heterocyclic ring systems are used frequently in organic synthesis and medicinal chemistry because of their broad spectrum of activities.[1]
2-pyrazoline derivatives were obtained from synthesized chalcones by refluxing in the presence of acidic medium (Figure 2)
When 1H nuclear magnetic resonance (NMR) spectra of pyrazoline derivatives were examined, three different characteristic signals belonging to the methylene group at position 4 (Ha and Hb) and the methine group at position 5 (Hx) of the pyrazoline ring were determined

Summary

Introduction

Pyrazoline scaffolds bearing five-membered heterocyclic ring systems are used frequently in organic synthesis and medicinal chemistry because of their broad spectrum of activities.[1] Pyrazoline rings have important pharmacological and biological properties such as antioxidant, anti-inflammatory, analgesic, antimicrobial, antimalarial, antihypertensive, anticonvulsant, antidepressant, anticancer.[2,3,4,5,6] We studied the synthesis and antiproliferative activity of some pyrazoline compounds in our previous study.[7] Pyrazolines exhibited these different activities by interacting with some receptors or enzymes. ElBordiny et al demonstrated in their study that pyrazolines are superior lipoxygenase enzyme inhibitors compared to the reference drug.[8] Chaudhry et al and Sathish et al reported pyrazoline derivatives as alpha-glucosidase inhibitors.[9,10] many studies proved different activities of pyrazoline derivatives as receptor tyrosine kinase, topoisomerase 1, carbonic anhydrase and cholinesterase inhibitors. It was found that nitrogen atoms of the pyrazoline ring and at least one substitution with aryl moiety are essential for anti-inflammatory activity (Gawad et al, 2012).[11,12,13,14,15]

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Conclusion