Synthesis of 3‐hydroxy‐2‐naphthohydrazide‐based hydrazones and their implications in diabetic management via in vitro and in silico approaches

Abstract

Diabetes mellitus (DM) has prevailed as a chronic health condition and has become a serious global health issue due to its numerous consequences and high prevalence. We have synthesized a series of hydrazone derivatives and tested their antidiabetic potential by inhibiting the essential carbohydrate catabolic enzyme, “α‐glucosidase.” Several approaches including fourier transform infrared, 1H NMR, and 13C NMR were utilized to confirm the structures of all the synthesized derivatives. In vitro analysis of compounds 3a–3p displayed more effective inhibitory activities against α‐glucosidase with IC50 in a range of 2.80–29.66 µM as compared with the commercially available inhibitor, acarbose (IC50 = 873.34 ± 1.67 M). Compound 3h showed the highest inhibitory potential with an IC50 value of 2.80 ± 0.03 µM, followed by 3i (IC50 = 4.13 ± 0.06 µM), 3f (IC50 = 5.18 ± 0.10 µM), 3c (IC50 = 5.42 ± 0.11 µM), 3g (IC50 = 6.17 ± 0.15 µM), 3d (IC50 = 6.76 ± 0.20 µM), 3a (IC50 = 9.59 ± 0.14 µM), and 3n (IC50 = 10.01 ± 0.42 µM). Kinetics analysis of the most potent compound 3h revealed a concentration‐dependent form of inhibition by 3h with Ki value = 4.76 ± 0.0068 µM. Additionally, an in silico docking approach was applied to predict the binding patterns of all the compounds, which indicates that the hydrazide and the naphthalene‐ol groups play a vital role in the binding of the compounds with the essential residues (i.e., Glu277 and Gln279) of the α‐glucosidase enzyme.

Novel N‐pyrocatechoyl and N‐pyrogalloyl hydrazone antioxidants endowed with cytotoxic and antibacterial activity

“…[ 11 ] Among many, hydrazone scaffold, including N ‐acylhydrazones, was identified as a privileged substrate in medicinal chemistry. [ 12–15 ] Fruitful explorations of hydrazone‐type derivatives exposed their various biological traits, [ 16 ] such as antitumor, [ 17 ] antiproliferative, [ 18 ] antioxidant, [ 19 ] antimicrobial, [ 20 ] antitubercular, [ 21 ] antileishmanial, [ 22 ] anti‐Alzheimer, [ 23 ] antidiabetic, [ 24 ] anti‐inflammatory, [ 25 ] anticonvulsant, [ 26 ] and so on. Also, the frequent employment of hydrazones in medicinal chemistry is welcomed due to simple synthetic methods feasible even without catalysts, as well as to straightforward chemical transformations and tunability.…”