Riaz_2015_Bioorg.Chem_63_64

This paper presents the efficient high yield synthesis of novel pyridine 2,4,6-tricarbohydrazide derivatives (4a-4i) along with their alpha-glucosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition activities. The enzymes inhibition results showed the potential of synthesized compounds in controlling both type-II diabetes mellitus and Alzheimer's disease. In vitro biological investigations revealed that most of compounds were more active against yeast alpha-glucosidase than the reference compound acarbose (IC50 38.25+/-0.12muM). Among the tested series the compound 4c bearing 4-flouro benzyl group was noted to be the most active (IC50 25.6+/-0.2muM) against alpha-glucosidase, and it displayed weak inhibition activities against AChE and BChE. Compound 4a exhibited the most desired results against all three enzymes, as it was significantly active against all the three enzymes; alpha-glucosidase (IC50 32.2+/-0.3muM), AChE (IC50 50.2+/-0.8muM) and BChE (IC50 43.8+/-0.8muM). Due to the most favorable activity of 4a against the tested enzymes, for molecular modeling studies this compound was selected to investigate its pattern of interaction with alpha-glucosidase and AChE targets.