Pyrazole Incorporated New Thiosemicarbazones: Design, Synthesis and Investigation of DPP-4 Inhibitory Effects
作者： Belgin Sever , Hasan Soybir , Şennur Görgülü , Zerrin Cantürk , Mehlika Dilek Altıntop
DOI: 10.3390/MOLECULES25215003
关键词:
摘要: Dipeptidyl peptidase-4 (DPP-4) inhibition has been recognized as a promising approach to develop safe and potent antidiabetic agents for the management of type 2 diabetes. In this context, new thiosemicarbazones (2a–o) were prepared efficiently by reaction aromatic aldehydes with 4-[4-(1H-pyrazol-1-yl)phenyl]thiosemicarbazide (1), which was obtained via 4-(1H-pyrazol-1-yl)phenyl isothiocyanate hydrazine hydrate. Compounds 2a–o evaluated their DPP-4 inhibitory effects based on convenient fluorescence-based assay. 4-[4-(1H-pyrazol-1-yl)phenyl]-1-(4-bromobenzylidene)thiosemicarbazide (2f) identified most effective inhibitor in series an IC50 value 1.266 ± 0.264 nM when compared sitagliptin (IC50 = 4.380 0.319 nM). MTT test carried out assess cytotoxic compounds NIH/3T3 mouse embryonic fibroblast (normal) cell line. According cytotoxicity assay, compound 2f showed towards line higher than 500 µM pointing its favourable safety profile. Molecular docking studies indicated that presented π-π interactions Arg358 Tyr666 pyrazole scaffold 4-bromophenyl substituent, respectively. Overall, vitro silico put emphasis attracts great notice drug-like further research.
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