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- B. Sc. Clinical Nutrition, Dietetics, and Food Science - Undergraduate
Publication Type : Journal Article
Publisher : Molecular Diversity, Springer science
Url : https://doi.org/10.1007/s11030-022-10577-4
Campus : Kochi
School : School of Pharmacy
Year : 2022
Abstract : A series of novel pyridazine-acetohydrazide hybrids were designed, synthesized, and evaluated for their in vitro and in vivo antihyperglycemic activity. In this context, pyridazine-acetohydrazides (6a-6p) were synthesized by coupling substituted aldehyde with 2-(5-cyano-6-oxo-3,4-diphenylpyridazine-1-6H-yl) acetohydrazide, which was prepared via the reaction of pyridazine ester with hydrazine hydrate. The molecular docking study was carried out to examine the binding affinities and interaction of designed compounds against the DPP-4 enzyme. Compounds 6e, 6f, 6l, and 6n exhibited interaction with active residue. In silico ADMET properties, and toxicity studies corroborated that compounds were found to have good bioavailability and less toxic. The synthesized compounds were further estimated for in vitro DPP-4 activity. Compounds 6e and 6l were found as the most effective DPP-4 inhibitor in this series with IC50 values (6.48, 8.22 nM) when compared with sitagliptin (13.02 nM). According to the toxicity assay compound, 6l showed very less toxicity at a higher concentration so further selected for the in vivo antihyperglycemic activity.
Cite this Research Publication : Manisha Nidhar, Vipin Kumar, Archisman Mahapatra, Priya Gupta, Brijesh Kumar Yadav, Rahul Kumar Singh, and Ashish Kumar Tewari, Ligand-based designing of DPP-4 inhibitors via hybridization; synthesis, docking, and biological evaluation of pyridazine-acetohydrazides, Molecular Diversity (2022). https://doi.org/10.1007/s 11030-022-10577-4.