Synthesis and biological evaluation of novel Trifluoromethylated Arylidene-hydrazinyl-thiazoles as neuroprotective agents.

Neurodegenerative diseases, a substantial global health challenge affecting millions, underscore the pressing need for novel and effective pharmacotherapeutic drugs to address these disorders. In this concern, a library of novel trifluoromethylated arylidene-hydrazinyl-thiazoles has been synthesized and assessed for their anti-neurodegenerative potential. Multicomponent regioselective chemical transformation has been carried out utilizing thiosemicarbazide, trifluoromethylated 1,3-diketones and heteroaryl aldehydes in the presence of N-bromosuccinimide (NBS) in refluxing ethanol. The regioisomeric structure of the synthesized products was unambiguously characterized by employing heteronuclear 2D NMR spectroscopic studies. All the synthesized derivatives were evaluated for their anti-neurodegenerative properties on rat brain hippocampus-derived Neural Stem Cells (NSCs), examining their impact on survival, proliferation and neuronal differentiation in vitro. Among the tested thiazole derivatives, compounds 4a, 4b, 4c, 4f, 4 g, 4b' and 4i' demonstrated a remarkable increase in the number of neuronal cells as compared to the control group within the NSC culture and also exhibited the ability to promote NSC differentiation towards the neuronal lineage. Additionally, the selected compounds showed protection against amyloid beta (Aβ)-induced neurotoxicity in NSCs culture. Incorporating the trifluoromethyl group into the thiazole scaffold is a pivotal factor in augmenting biopotency, resulting in a marked increase in the count of neuronal cells compared to their non-fluorinated thiazole counterparts.