Synthesis and structure-activity relationship studies of benzimidazole-thioquinoline derivatives as α-glucosidase inhibitors

被引：29

作者：

Farid, Sara Moghadam ^{[1
]}

Noori, Milad ^{[1
]}

Montazer, Mohammad Nazari ^{[1
]}

Khalili Ghomi, Minoo ^{[1
]}

Mollazadeh, Marjan ^{[1
]}

Dastyafteh, Navid ^{[1
]}

Irajie, Cambyz ^{[2
]}

Zomorodian, Kamiar ^{[3
]}

Mirfazli, Seyedeh Sara ^{[4
]}

Mojtabavi, Somayeh ^{[5
]}

Faramarzi, Mohammad Ali ^{[5
]}

Larijani, Bagher ^{[1
]}

Iraji, Aida ^{[6
,7
]}

Mahdavi, Mohammad ^{[1
]}

机构：

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

[2] Shiraz Univ Med Sci, Sch Adv Med Sci & Technol, Dept Med Biotechnol, Shiraz, Iran

[3] Shiraz Univ Med Sci, Sch Med, Dept Med Mycol & Parasitol, Shiraz, Iran

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

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

[6] Shiraz Univ Med Sci, Stem Cells Technol Res Ctr, Shiraz, Iran

[7] Shiraz Univ Med Sci, Cent Res Lab, Shiraz, Iran

来源：

SCIENTIFIC REPORTS | 2023年 / 13卷 / 01期

关键词：

IN-VITRO EVALUATION; BIOLOGICAL EVALUATION; MOLECULAR DOCKING; CYTOCHROME-P450; DESIGN; SILICO;

D O I：

10.1038/s41598-023-31080-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

In this article, different s-substituted benzimidazole-thioquinoline derivatives were designed, synthesized, and evaluated for their possible alpha-glucosidase inhibitory activities. The most active compound in this series, 6j (X = 4-bromobenzyl) exhibited significant potency with an IC50 value of 28.0 +/- 0.6 mu M compared to acarbose as the positive control with an IC50 value of 750.0 mu M. The kinetic study showed a competitive inhibition pattern against alpha-glucosidase for the 6j derivative. Also, the molecular dynamic simulations were performed to determine key interactions between compounds and the targeted enzyme. The in silico pharmacodynamics and ADMET properties were executed to illustrate the druggability of the novel derivatives. In general, it can be concluded that these derivatives can serve as promising leads to the design of potential alpha-glucosidase inhibitors.

引用

页数：14

共 44 条

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