A potent gelatinase inhibitor with anti-tumor-invasive activity and its metabolic disposition.
A potent gelatinase inhibitor with anti-tumor-invasive activity and its metabolic disposition.
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DOI：
10.1111/j.1747-0285.2008.00750.x
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发表时间：
2009-02
影响因子：
3
通讯作者：
Chang M
中科院分区：
文献类型：
--
作者：
Lee M;Celenza G;Boggess B;Blase J;Shi Q;Toth M;Bernardo MM;Wolter WR;Suckow MA;Hesek D;Noll BC;Fridman R;Mobashery S;Chang M
转移性肿瘤导致超过90%的死亡率。尽管肿瘤的侵袭性对不良疾病结果的重要性，但还没有抗侵袭性化合物被商业化。我们在本文中描述了4-（4-（硫杂丙烷基甲基磺酰基）苯氧基）-苯基甲磺酸盐（化合物2）的合成和评估，其作为明胶酶（基质金属蛋白酶-2和-9）的有效且选择性抑制剂，这两种酶与肿瘤的侵袭性有关。证明化合物2显著减弱人纤维肉瘤细胞（HT 1080）的侵袭性。化合物2的代谢涉及在α-亚甲基处的羟基化，其产生亚磺酸、硫杂丙环开环，随后甲基化和氧化，以及硫杂丙环和苯环两者的半胱氨酸缀合。
Metastatic tumors lead to more than 90% fatality. Despite the importance of invasiveness of tumors to poor disease outcome, no anti-invasive compounds have been commercialized. We describe herein the synthesis and evaluation of 4-(4-(thiiranylmethylsulfonyl)phenoxy)-phenyl methane-sulfonate (compound 2) as a potent and selective inhibitor of gelatinases (matrix metalloproteinases-2 and -9), two enzymes implicated in invasiveness of tumors. It was demonstrated that compound 2 significantly attenuated the invasiveness of human fibrosarcoma cells (HT1080). The metabolism of compound 2 involved hydroxylation at the a-methylene, which generates sulfinic acid, thiirane ring-opening, followed by methylation and oxidation, and cysteine conjugation of both the thiirane and phenyl rings.
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影响因子：
3
作者：
Celenza, Giuseppe;Villegas-Estrada, Adriel;Chang, Mayland
通讯作者：
Chang, Mayland
影响因子：
5.2
作者：
Ma, DW;Cai, Q
通讯作者：
Cai, Q
影响因子：
11.2
作者：
Krüger, A;Arlt, MJE;Fridman, R
通讯作者：
Fridman, R
影响因子：
3.9
作者：
Chen, Q;Doss, GA;Tang, W
通讯作者：
Tang, W
影响因子：
6.4
作者：
Bonfil, RD;Sabbota, A;Fridman, R
通讯作者：
Fridman, R