Phenothiazine-based chalcones as potential dual-target inhibitors toward cholinesterases (AChE,BuChE) and monoamine oxidases (MAO-A,MAO-B) |
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| Authors: | Cem Yamali Feyza Sena Engin Sinan Bilginer Mehtap Tugrak Dilan Ozmen Ozgun Gulsen Ozli Serkan Levent Begum Nurpelin Saglik Yusuf Ozkay Halise Inci Gul |
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| Institution: | 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Agri Ibrahim Cecen University, Agri, Turkey;3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erzincan University, Erzincan, Turkey;4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey |
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| Abstract: | Chalcones targeting neurodegenerative diseases have been known as attractive structures in drug design and discovery. In this study, phenothiazine-based chalcones as ChEs and MAOs inhibitors were designed and synthesized via base-catalyzed Claisen-Schmidt condensation, and chemical structures of the compounds were elucidated by NMRs and HRMS. Compounds 3 and 9 showed promising inhibition potency against AChE enzyme with IC50 values of 0.221 μM and 0.053 μM while compound 9 displayed remarkable inhibition potency toward MAO-B enzyme with IC50 value of 0.048 μM. Compound 9 , as a dual-target inhibitor, selectively inhibited AChE and MAO-B enzymes. This promising behavior is an advantage for the compound since MAO-B and AChE inhibition have a role in Alzheimer's disease. Fused tricyclic ring systems such as phenothiazine incorporated with chalcone moiety being multitargeting ligands may help scientists for the rational design of novel lead compounds targeting neurodegenerative illnesses. |
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