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

被引：11

作者：

Ahmed, Kainat ^{[1
]}

Bashir, Maryam ^{[2
]}

Bano, Rehana ^{[2
]}

Sarfraz, Muhammad ^{[3
]}

Khan, Hidayat Ullah ^{[4
]}

Khan, Shahnaz ^{[4
]}

Sharif, Ahsan ^{[2
]}

Waseem, Amir ^{[5
]}

Gilani, Mazhar Amjad ^{[6
]}

Batool, Komal ^{[2
]}

Idrees, Rabia ^{[2
]}

Rauf, Abdul ^{[3
]}

Saleem, Rahman Shah Zaib ^{[1
]}

Arshad, Muhammad ^{[3
]}

机构：

[1] Lahore Univ Management Sci, Dept Chem & Chem Engn, SBASSE, DHA, Phase-5, Lahore 54792, Pakistan

[2] Univ Punjab, Ctr Organ Chem, Sch Chem, Lahore 54590, Pakistan

[3] Islamia Univ Bahawalpur, Inst Chem, Bahawalpur 63100, Pakistan

[4] Univ Sci & Technol, Dept Chem, Bannu 28100, Pakistan

[5] Quaid I Azam Univ, Dept Chem, Islamabad, Pakistan

[6] COMSATS Univ Islamabad, Dept Chem, Lahore Campus, Islamabad, Pakistan

来源：

JOURNAL OF MOLECULAR STRUCTURE | 2023年 / 1284卷

关键词：

4-triazine; Hydrazone; Heteroaromatic aldehyde; Cholinesterase; Anti-oxidant; DFT; molecular docking; DENSITY-FUNCTIONAL THEORY; BIOLOGICAL EVALUATION; ANTIFUNGAL ACTIVITY; UREASE INHIBITION; DERIVATIVES; DESIGN; ANALOGS; SERIES; ASSAY;

D O I：

10.1016/j.molstruc.2023.135383

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

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.

引用

页数：13

共 63 条

[41] Natural products and their derivatives as cholinesterase inhibitors in the treatment of neurodegenerative disorders: An update [J].