Potansiyel Tedavi Olarak Parkinson Hastalığının Vitro Modelinde Yeni Sentezlenmiş Chalcone Türevlerinin PC12 Hücreleri Üzerindeki Etkisinin Değerlendirilmesi

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Chalcone is a common simple scaffold found in many naturally occurring compounds. Many Chalcone derivatives have also been prepared due to their convenient synthesis. These natural products and synthetic compounds have shown numerous interesting biological activities, such as antioxidant, anti-inflammatory, induction of apoptosis, and angiogenesis. As the second most common neurodegenerative disease after Alzheimer's disease, Parkinson’s disease is most common motor function disorder. Even though this disease is not fully understood, processes such as oxidative stress and neuronal apoptosis are largely involved in its progress. As such, antioxidants are significant agents in slowing down the process through running interference in ROS production and apoptosis. Here, we present the effect of three newly synthesized Chalcone compounds on 6-OHDA-induced cytotoxicity on the PC12 cells in Parkinson's disease model by integrating several experimental (MTT assay, ROS assay, Annexin & PI assay, Western blotting P53, Bax, Bcl2) data and validating the results based on the interactional contribution equations of these compounds obtained from previous experimental and theoretical study carried out on the molecular resonance and interactional behavior of these compounds via Linear solvation energy relationship (LSER) model and time-dependent density functional theory and configuration interaction calculations. We conclude that all three Chalcones have neuroprotective activity, and presented a reduction in ROS production and an increment in cell viability in the groups treated with 6-OHDA. This effect was observed at lower concentrations for all Chalcone compounds. At higher concentrations Chalcones 1 and 2 showed cytotoxicity. However, Chalcone 3 did not show any cytotoxicity, even for high doses, which points out the therapeutic potential of this Chalcone in reducing the dopaminergic cell destruction.

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