Design, synthesis, and evaluation of novel bistrifluoromethyl-based hydrazones as dual inhibitors of acetylcholinesterase and carbonic anhydrase enzymes for Alzheimer's disease.

In this project, non-sulfonamide bistrifluoromethyl-derived hydrazide-hydrazones were synthesized as multi-target-directed ligands to treat Alzheimer's disease and then, the novel derivatives were characterized by diverse spectral methods. Acetylcholinesterase (AChE), and human carbonic anhydrase (hCA) inhibitory qualifications of these compounds were determined. The reported compounds (2a-y) were determined to be effective inhibitors of the hCA I, hCA II and AChE enzymes with Ki values in the range of 1.130 ± 0.15-5.440 ± 0.93 µM for hCA I, 0.894 ± 0.05-6.647 ± 1.35 µM for hCA II, and 0.196 ± 0.03-4.222 ± 1.04 µM for AChE. In silico studies were also performed to illuminate the binding interactions.

Antioxidant activity of novel imidazo[2,1-b]thiazole derivatives: Design, synthesis, biological evaluation, molecular docking study and in silico ADME prediction.

A series of novel oxo-hydrazone and spirocondensed-thiazolidine derivatives of imidazo[2,1-b]thiazole were synthesized and evaluated for their antioxidant activity. The antioxidant activity of 18 newly synthesized compounds and 12 previously reported compounds bearing similar scaffold, were evaluated by three different methods: inhibition of FeCl3/ascorbate system-induced lipid peroxidation of lecithin liposome (anti-LPO), scavenging activity against ABTS radical and Ferric Reducing Antioxidant Power (FRAP) activity. 4h, 5h, and 6h displayed the highest anti-LPO and ABTS radical removal activity. Also, in FRAP analysis, 4i and 4a displayed the best activity. In addition to the in vitro analysis, docking studies targeting the active site of Human peroxiredoxin 5 (PDB ID: 1HD2) were employed to explore the possible interactions of these compounds with the receptor. Structure-activity relationships, as well as virtual ADME studies, were carried out and a relationship between biological, electronic, and physicochemical qualifications of the target compounds was determined.

Design and synthesis of novel Imidazo[2,1-b]thiazole derivatives as potent antiviral and antimycobacterial agents.

A series of novel acyl-hydrazone (4a-d) and spirothiazolidinone (5a-d, 6a-d) derivatives of imidazo[2,1-b]thiazole were synthesized and evaluated for their antiviral and antimycobacterial activity. The antituberculosis activity was evaluated by using the Microplate Alamar Blue Assay and the antiviral activity was evaluated against diverse viruses in mammalian cell cultures. According to the biological activity studies of the compounds, 5a-c displayed hope promising antitubercular activity, 6d was found as potent for Coxsackie B4 virus, 5d was found as effective against Feline corona and Feline herpes viruses. Consequently, the obtained results displayed that, 5a-d and 6d present a leading structure for future drug development due to its straightforward synthesis and relevant bioactivity.