Design and synthesis of new fused carbazole-imidazole derivatives as anti-diabetic agents: In vitro α-glucosidase inhibition, kinetic, and in silico studies

被引：48

作者：

Adib, Mehdi ^{[1
]}

Peytam, Fariba ^{[1
]}

Shourgeshty, Reihaneh ^{[1
]}

Mohammadi-Khanaposhtani, Maryam ^{[2
]}

Jahani, Mehdi ^{[1
]}

Imanparast, Somaye ^{[3
,4
]}

Faramarzi, Mohammad Ali ^{[3
,4
]}

Larijani, Bagher ^{[5
]}

Moghadamnia, Ali Akbar ^{[2
,6
]}

Esfahani, Ensieh Nasli ^{[7
]}

Bandarian, Fatemeh ^{[7
]}

Mahdavi, Mohammad ^{[5
]}

机构：

[1] Univ Tehran, Coll Sci, Sch Chem, POB 14155-6455, Tehran, Iran

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

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

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

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

[6] Babol Univ Med Sci, Dept Pharmacol, Fac Med Sci, Babol Sar, Iran

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2019年 / 29卷 / 05期

关键词：

Carbazole; Imidazole; alpha-Glucosidase; In silico study; In vitro evaluation; EFFICIENT; POTENT;

D O I：

10.1016/j.bmcl.2019.01.012

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

Twenty three fused carbazole-imidazoles 6a-w were designed, synthesized, and screened as new alpha-glucosidase inhibitors. All the synthesized fused carbazole-imidazoles 6a-w were found to be more active than acarbose (IC50 = 750.0 +/- 1.5 mu M) against yeast alpha-glucosidase with IC50 values in the range of 74.0 +/- 0.7-298.3 +/- 0.9 mu M. Kinetic study of the most potent compound 6v demonstrated that this compound is a competitive inhibitor for alpha-glucosidase (K-i value = 75 mu M). Furthermore, the in silico studies of the most potent compounds 6v and 6o confirmed that these compounds interacted with the key residues in the active site of alpha-glucosidase.

引用

页码：713 / 718

页数：6

共 23 条

[1]

Design, synthesis and in vitro -glucosidase inhibition of novel coumarin-pyridines as potent antidiabetic agents [J].