Synthesis, structure determination, biological activity and molecular modeling studies of novel imidazothiazole derivatives

In this study, a series of novel hydrazinecarbothioamide (thiosemicarbazide) (4a-r) and 1,2,4-triazole-3-thione (5a-p) derivatives bearing imidazo[2,1-b]thiazole moiety, were synthesized. The molecular structures of the synthesized compounds were illuminated by diverse analytical and spectral methods. In vitro antioxidant activities, α-glucosidase and AChE enzyme inhibition activities of the compounds were performed. Ferric-Reducing antioxidant power (FRAP) and DPPH radical scavenging activity of the compounds were determined for the evaluation of their antioxidant activities. Within the synthesized compounds, 4i, 4j, 4k, 4n and 4o displayed the highest DPPH radical scavenging activity. Besides, 4i, 4j, 4k, 4o and 5l were determined as possessing the highest FRAP values. The α-glucosidase enzyme inhibition activities of 4l, 4p, 5d, 5g, 5h and 5l were found 68.85 – 1.41 times better than the reference compound Acarbose. 4h displayed the best AChE inhibitory activity among the synthesized compounds. In addition to the in vitro analyzes, docking studies targeting the active site of Human Peroxiredoxin 5 (PDB ID: 1HD2), N-terminal Human Maltase-Glucoamylase (PDB ID: 3CTT) and AChE (PDB ID: 1DX6) were performed and the interactions between the synthesized compounds and target receptors were elucidated. In silico Pharmacokinetic characteristics of the novel compounds were evaluated by conducting virtual ADME studies.