Synthesis, Spectroscopic Characterization, DFT, Molecular Docking and Antidiabetic Activity of N-Isonicotinoyl Arylaldehyde Hydrazones

Abstract

Two N-isonicotinoyl arylaldehyde hydrazones named N'-(4-fluorobenzylidene)isonicotinohydrazide (2a) N'-(4-methylbenzylidene)isonicotinohydrazide (2 b) have been synthesized and characterized utilizing spectroscopic techniques and X-ray diffraction. The s-cis isomeric geometry of 2a and 2 b is confirmed by comparing the observed stretching bond of the azomethine group with their corresponding calculated ones of s-cis and s-trans isomers for both 2a and 2 b. The s-cis geometry is in good accordance with the one obtained by X-ray techniques. The global and local electronic properties of 2a and 2 b were determined at the B3LYP/6-311 + G(d,p) level of theory. The Results reveal that the stability of s-cis isomers compared to s-trans ones is mainly refer to the intramolecular carbon-hydrogen bonding formed between lone pairs of the carbonyl group and the hydrogen atom of azomethine of 2.15 Å. The antidiabetic activity of 2a and 2 b is investigated by determining their potency to inhibit α-glucosidase. 2a and 2 b showed higher inhibitory toward α-glucosidase as compared to the reference drug acarbose. Molecular docking of 2a and 2 b into the active site of α-glucosidase showed that the higher inhibition efficiency of 2 b compared to 2a is mainly refers to the stability of 2 b-(α-glucosidase) complex compared with 2a-(α-glucosidase).