A structure-activity relationship study of 1,2,4-triazolo[1,5-a][1,3,5]triazin-5,7-dione and its 5-thioxo analogues on anti-thymidine phosphorylase and associated anti-angiogenic activities

被引：29

作者：

Bera, Hriday ^{[1
,2
]}

Tan, Bee Jen ^{[2
]}

Sun, Lingyi ^{[2
]}

Dolzhenko, Anton V. ^{[2
,3
]}

Chui, Wai-Keung ^{[2
]}

Chiu, Gigi Nagar Chee ^{[2
]}

机构：

[1] Gokaraju Rangaraju Coll Pharm, Hyderabad 500090, Andhra Pradesh, India

[2] Natl Univ Singapore, Fac Sci, Dept Pharm, Singapore 117543, Singapore

[3] Monash Univ, Sch Pharm, Bandar Sunway 46150, Selangor, Malaysia

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 67卷

基金：

英国医学研究理事会;

关键词：

1,2,4-Triazolo[1,5-a][1,3,5]triazine; Thymidine phosphorylase inhibitors; SAR; Mixed-type inhibition; Breast cancer; Anti-angiogenesis; ENDOTHELIAL GROWTH-FACTOR; TUMOR ANGIOGENESIS; NUCLEOSIDE DERIVATIVES; BREAST-CARCINOMA; INHIBITORS; 3(5)-AMINO-1,2,4-TRIAZOLES; EXPRESSION; CANCER;

D O I：

10.1016/j.ejmech.2013.06.051

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Thirty-three 1,2,4-triazolo[1,5-a][1,3,5]triazin-5,7-dione and its 5-thioxo analogues were designed and synthesized which contained different substituents at meta- and/or para-positions of 2-phenyl or 2-benzyl ring attached to the fused ring structure. The preliminary pharmacological evaluation demonstrated that the 5-thioxo analogues of 1,2,4-triazolo[1,5-a][1,3,5]triazine exhibited a varying degree of inhibitory activity towards thymidine phosphorylase, comparable or better than reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value = 42.63 mu M). Moreover, compounds 5q and 6i displayed a mixed-type of inhibitory mechanism in the presence of variable concentrations of thymidine (dThd). In addition, selected compounds were found to have a noticeable inhibitory effect on the expression of angiogenesis markers, including VEGF and MMP-9 in MDA-MB-231 breast cancer cells. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：325 / 334

页数：10

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