Design, Synthesis, and Neuroprotective Effects of a Series of Pyrazolines against 6-Hydroxydopamine-Induced Oxidative Stress

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Ahmet ÖzdemirMiriş Dikmen

Abstract

Parkinson's disease (PD) is a chronic, progressive, and age-related neurodegenerative disorder characterized by the loss of midbrain dopaminergic neurons caused by the accumulation of free radicals and oxidative stress. Based on the neuroprotective properties of 2-pyrazoline derivatives, in the current work, 1-(phenyl/4-substituted phenyl)-3-(2-furanyl/thienyl)-5-aryl-2-pyrazolines (3a⁻i, 4a⁻i) were synthesized via the cyclization of the chalcones (1, 2) with suitable phenylhydrazine hydrochloride derivatives. All these compounds were investigated for their neuroprotective effects using an in vitro 6-hydroxydopamine (6-OHDA)-induced neurotoxicity model of PD in the rat pheochromocytoma (PC-12) Adh cell line. In addition, some different pharmacokinetic parameters of all compounds were in silico predicted by the QikProp module of Schrödinger's Maestro molecular modeling package. 4-Methylsulfonylphenyl substituted compounds 3h (20%) and 4h (23%) were determined as the most promising neuroprotective agents related to their inductive roles in cell viability when compared with the 6-OHDA-positive control group (43% and 42%, respectively). Moreover, in silico pharmacokinetic results indicated that all compounds were within the accepta...Continue Reading

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Citations

Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Svetlana A PopovaAleksandr V Kutchin

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Methods Mentioned

BETA
pharmacotherapy

Software Mentioned

QikProp
Graphpad Prism

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