Potent heteroaromatic hydrazone based 1,2,4-triazine motifs: synthesis, anti-oxidant activity, cholinesterase inhibition, quantum chemical and molecular docking studies

1,2,4-Triazine based hydrazone scaffolds possessing impressive biological activities are synthesized using heteroaromatic aldehydes. The target molecules were characterized by detailed spectroscopic techniques. Anti-oxidant capacities of target compounds were determined using DPPH free radical scavenging ac-tivity, ABTS method and superoxide anion scavenging assay by means of NBT. Compound 4a displayed potent anti-oxidant potential against ABTS having IC50 28.09 & PLUSMN; 0.15 & mu;M comparative to the standard Trolox (26.01 & PLUSMN; 0.02 & mu;M). Cholinesterase inhibitory potentials of the synthesized compounds were also evaluated, where compound 4b intensely inhibited against AChE and BChE in dose dependent method compared to standard drugs, allanzanthane and galantamine. The IC50 value of compound 4b for AChE was 15.24 & PLUSMN; 0.03 & mu;M vs 10.13 & PLUSMN; 0.01 for allanzanthane and 13.01 & PLUSMN; 0.02 for galantamine, whereas, IC50 value of 4b for BChE was 17.01 & PLUSMN; 0.6 & mu;M vs 22.00 & PLUSMN; 0.01 for allanzanthane and 26.02 & PLUSMN; 0.09 for galan-tamine. Density functional theory (DFT) simulations of synthesized compounds ( 4a-c ) complement the experimental spectroscopic data (FTIR, 1 H & 13 C NMR & UV-Visible). The HOMO-LUMO energy gaps of 3.58 eV to 3.80 eV reflect the kinetic stability of the compounds ( 4a-c ). Moreover, the MEP analysis con-firmed the chemical reactivities of these compounds and more nucleophilic sites were identified at the heteroatoms of heterocyclic moiety and triazine moiety. In silico molecular docking study revealed that our active targeted compounds have minimum binding energy and good affinity toward the active pocket of target protein. These results showed that our synthesized compounds are excellent inhibitors of AChE & BChE enzymes, and therefore, can be subjected to further studies in order to accomplish potent drug responsible for the treatment of Alzheimer's disease.& COPY; 2023 Elsevier B.V. All rights reserved.