Synthesis, biological activities, and molecular docking studies of triazolo[4,3-b]triazine derivatives as a novel class of α-glucosidase and α-amylase inhibitors

被引：8

作者：

Seyfi, Soheila ^{[1
]}

Salarinejad, Somayeh ^{[2
]}

Moghimi, Setareh ^{[1
]}

Toolabi, Mahsa ^{[3
]}

Sadeghian, Nastaran ^{[4
]}

Tuezuen, Burak ^{[5
]}

Firoozpour, Loghman ^{[1
,2
]}

Ketabforoosh, Shima H. M. E. ^{[6
]}

Taslimi, Parham ^{[4
,7
]}

Foroumadi, Alireza ^{[1
,2
]}

机构：

[1] Univ Tehran Med Sci, Inst Pharmaceut Sci TIPS, Drug Design & Dev Res Ctr, Tehran, Iran

[2] Univ Tehran Med Sci, Fac Pharm, Dept Med Chem, Tehran, Iran

[3] Ahvaz Jundishapur Univ Med Sci, Sch Pharm, Dept Med Chem, Ahvaz, Iran

[4] Bartin Univ, Fac Sci, Dept Biotechnol, Bartin, Turkiye

[5] Sivas Cumhuriyet Univ, Tech Sci Vocat Sch Sivas, Plant & Anim Prod Dept, Sivas, Turkiye

[6] Alborz Univ Med Sci, Sch Pharm, Dept Med Chem, Karaj, Iran

[7] Bartin Univ, Fac Sci, Dept Biotechnol, TR-74100 Bartin, Turkiye

来源：

ARCHIV DER PHARMAZIE | 2024年 / 357卷 / 07期

关键词：

alpha-amylase; alpha-glucosidase; diabetes; molecular docking; 1,2,4-TRIAZINE DERIVATIVES; SYNERGETIC INHIBITION; GENISTEIN; ANALOGS; DESIGN;

D O I：

10.1002/ardp.202300628

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In diabetes mellitus, amylase and glucosidase enzymes are the primary triggers. The main function of these enzymes is to break macromolecules into simple sugar units, which directly affect blood sugar levels by increasing blood permeability. To overcome this metabolic effect, there is a need for a potent and effective inhibitor capable of suppressing the enzymatic conversion of sugar macromolecules into their smaller units. Herein, we reported the discovery of a series of substituted triazolo[4,3-b][1,2,4]triazine derivatives as alpha-glucosidase and alpha-amylase inhibitors. All target compounds demonstrated significant inhibitory activities against alpha-glucosidase and alpha-amylase enzymes compared with acarbose as the positive control. The most potent compound 10k, 2-[(6-phenyl-[1,2,4]triazolo[4,3-b][1,2,4]triazin-3-yl)thio]-N-[4-(trifluoromethyl)phenyl]acetamide, demonstrated IC50 values of 31.87 and 24.64 nM against alpha-glucosidase and alpha-amylase enzymes, respectively. To study their mechanism of action, kinetic studies were also done, which determined the mode of inhibition of both enzymes. Molecular docking was used to confirm the binding interactions of the most active compounds.

引用

页数：15