Structure-based design, synthesis, molecular docking study and biological evaluation of 1,2,4-triazine derivatives acting as COX/15-LOX inhibitors with anti-oxidant activities

被引：20

作者：

Khoshneviszadeh, Mehdi ^{[1
,2
]}

Shahraki, Omolbanin ^{[2
]}

Khoshneviszadeh, Mahsima ^{[1
]}

Foroumadi, Alireza ^{[3
]}

Firuzi, Omidreza ^{[1
]}

Edraki, Najmeh ^{[1
]}

Nadri, Hamid ^{[4
]}

Moradi, Alireza ^{[4
]}

Shafiee, Abbas ^{[5
,6
]}

Miri, Ramin ^{[1
]}

机构：

[1] Shiraz Univ Med Sci, Med & Nat Prod Chem Res Ctr, Shiraz, Iran

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

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

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

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

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

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2016年 / 31卷 / 06期

关键词：

Cyclooxygenase; FRAP assay; 15-lipoxygenase; molecular modeling; 1,2,4-triazine; SELECTIVE CYCLOOXYGENASE-2 INHIBITORS; COX-2; INHIBITORS; ANTIINFLAMMATORY AGENTS; DISCOVERY; DRUGS; RESVERATROL; BEARING; MOIETY; POTENT; ACID;

D O I：

10.3109/14756366.2016.1158713

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 set of 1,2,4-triazine derivatives were designed as cyclooxygenase-2 (COX-2) inhibitors. These compounds were synthesized and screened for inhibition of cyclooxygenases (COX-1 and COX-2) based on a cellular assay using human whole blood (HWB) and lipoxygenase (LOX-15) that are key enzymes in inFammation. The results showed that 3-(2-(benzo[d][1,3]dioxol-5-ylmethylene) hydrazinyl)-5,6-bis(4-methoxyphenyl)-1,2,4-triazine (G11) was identified as the most potent COX-2 inhibitor (78%) relative to COX-1 (50%). Ferric reducing anti-oxidant power (FRAP) assay revealed that compound G10 possesses the highest anti-oxidant activity. The compound G3 with IC50 value of 124 mu M was the most potent compound in LOX inhibitory assay. Molecular docking was performed and a good agreement was observed between computational and experimental results.

引用

页码：1602 / 1611

页数：10

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