Synthesis and SAR study of 4,5-diaryl-1H-imidazole-2(3H)-thione derivatives, as potent 15-lipoxygenase inhibitors

被引：27

作者：

Assadieskandar, Amir ^{[1
,2
]}

Amini, Mohsen ^{[1
,2
]}

Salehi, Marjan ^{[1
,2
]}

Sadeghian, Hamid ^{[3
,4
]}

Alimardani, Maliheh ^{[4
]}

Sakhteman, Amirhossein ^{[5
]}

Nadri, Hamid ^{[5
]}

Shafiee, Abbas ^{[1
,6
]}

机构：

[1] Univ Tehran Med Sci, Fac Pharm, Dept Med Chem, Tehran 14176, Iran

[2] Univ Tehran Med Sci, Drug Design & Dev Res Ctr, Tehran 14176, Iran

[3] Mashhad Univ Med Sci, Buali Res Inst, Microbiol & Virol Res Ctr, Mashhad, Iran

[4] Mashhad Univ Med Sci, Sch Paramed Sci, Dept Lab Sci, Mashhad, Iran

[5] Shahid Sadoughi Univ Med Sci, Fac Pharm, Dept Med Chem, Yazd, Iran

[6] Univ Tehran Med Sci, Pharmaceut Sci Res Ctr, Tehran 14176, Iran

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 24期

关键词：

Soybean 15-lipoxygenase (SLO); Radical scavenging activity; Structure-activity relationship studies; 4,5-Diarylimidazole; 3-DIMENSIONAL STRUCTURE; LIPOXYGENASE; DESIGN; EXPRESSION; ATHEROSCLEROSIS; BENZOINS; COX-2;

D O I：

10.1016/j.bmc.2012.09.050

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 series of 4,5-diaryl-1H-imidazole-2(3H)-thione was synthesized and their inhibitory potency against soybean 15-lipoxygenase and free radical scavenging activities were determined. Compound 11 showed the best IC50 for 15-LOX inhibition (IC50 = 4.7 mu M) and free radical scavenging activity (IC50 = 14 mu M). Methylation of SH at C-2 position of imidazole has dramatically decreased the 15-LOX inhibition and radical scavenging activity as it can be observed in the inactive compound 14 (IC50 >250 mu M). Structure activity similarity (SAS) showed that the most important chemical modification in this series was methylation of SH group and Docking studies revealed a proper orientation for SH group towards Fe core of the 15-LOX active site. Therefore it was concluded that iron chelating could be a possible mechanism for enzyme inhibition in this series of compounds. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：7160 / 7166

页数：7

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