Design and synthesis of novel quinazolinone-1,2,3-triazole hybrids as new anti-diabetic agents: In vitro α-glucosidase inhibition, kinetic, and docking study

被引：144

作者：

Saeedi, Mina ^{[1
,2
]}

Mohammadi-Khanaposhtani, Maryam ^{[3
]}

Pourrabia, Parvaneh ^{[2
]}

Razzaghi, Nima ^{[4
]}

Ghadimi, Reza ^{[5
]}

Imanparast, Somaye ^{[6
,7
]}

Faramarzi, Mohammad Ali ^{[6
,7
]}

Bandarian, Fatemeh ^{[8
]}

Esfahani, Ensieh Nasli ^{[8
]}

Safavi, Maliheh ^{[9
]}

Rastegar, Hossein ^{[10
]}

Larijani, Bagher ^{[11
]}

Mandavi, Mohammad ^{[11
]}

Akbarzadeh, Tahmineh ^{[2
,4
]}

机构：

[1] Univ Tehran Med Sci, Med Plants Res Ctr, Fac Pharm, Tehran, Iran

[2] Univ Tehran Med Sci, Persian Med & Pharm Res Ctr, Tehran, Iran

[3] Babol Univ Med Sci, Cellular & Mol Biol Res Ctr, Hlth Res Inst, Babol Sar, Iran

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

[5] Babol Univ Med Sci, Social Determinants Hlth Res Ctr, Hlth Res Inst, Babol Sar, Iran

[6] Univ Tehran Med Sci, Dept Pharmaceut Biotechnol, Fac Pharm, Tehran, Iran

[7] Univ Tehran Med Sci, Biotechnol Res Ctr, Tehran, Iran

[8] Univ Tehran Med Sci, Diabet Res Ctr, Endocrinol & Metab Clin Sci Inst, Tehran, Iran

[9] Iranian Res Org Sci & Technol, Dept Biotechnol, POB 3353-5111, Tehran, Iran

[10] MOHE, Food & Drug Adm, Food & Drug Res Inst, Tehran, Iran

[11] Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Endocrinol & Metab Clin Sci Inst, Tehran, Iran

来源：

BIOORGANIC CHEMISTRY | 2019年 / 83卷

关键词：

Anti-diabetic activity; Competitive inhibition; alpha-Glucosidase; Molecular docking; Quinazolinone; 1,2,3-Triazole; BIOLOGICAL EVALUATION; MOLECULAR DOCKING; DERIVATIVES; 1,2,3-TRIAZOLES;

D O I：

10.1016/j.bioorg.2018.10.023

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A novel series of quinazolinone-1,2,3-triazole hybrids 10a-p were designed, synthesized, and evaluated for their in vitro alpha-glucosidase inhibitory activity leading to efficient anti-diabetic agents. All synthesized compounds exhibited good inhibitory activity against yeast alpha-glucosidase (IC50 values in the range of 181.0-474.5 mu M) even much more potent than standard drug acarbose (IC50 = 750.0). Among them, quinazolinone-1,2,3-triazoles possessing 4-bromobenzyl moiety connected to 1,2,3-triazole ring (10g and 10p) demonstrated the most potent inhibitory activity towards alpha-glucosidase. Compound 10g inhibited alpha-glucosidase in a competitive manner with K-i value of 117 mu M. Furthermore, the binding modes of the most potent compounds 10g and 10p in the alpha-aglucosidase active site was studied through in silico docking studies. Also, lack of cytotoxicity of compounds 10g and 10p was confirmed via MTT assay.

引用

页码：161 / 169

页数：9

共 29 条

[1] New 6-amino-pyrido[2,3-d]pyrimidine-2,4-diones as novel agents to treat type 2 diabetes: A simple and efficient synthesis, α-glucosidase inhibition, molecular modeling and kinetic study [J].