Synthesis, in vitro structure-activity relationship, and in vivo studies of 2-arylthiazolidine-4-carboxylic acid amides as anticancer agents.
Synthesis, in vitro structure-activity relationship, and in vivo studies of 2-arylthiazolidine-4-carboxylic acid amides as anticancer agents.
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DOI：
10.1016/j.bmc.2009.12.020
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发表时间：
2010-01-15
影响因子：
3.5
通讯作者：
Miller DD
中科院分区：
文献类型：
--
作者：
Lu Y;Wang Z;Li CM;Chen J;Dalton JT;Li W;Miller DD
合成了一系列（2RS，4R）-2-芳基噻唑烷-4-羧酸酰胺（ATCAA）。与对照细胞（分别为成纤维细胞和RH7777）相比，针对黑色素瘤和前列腺癌细胞的抗增生活性进行了评估。化合物3ID对三种黑色素瘤细胞系（B16-F1，A375和WM-164）表现出最佳的选择性和抑制活性。化合物15B和3AC对四个前列腺癌细胞系（DU 145，PC-3，LNCAP和PPC-1）具有良好的选择性和效力。讨论了侧链，噻唑烷环和苯基取代基的结构活性关系（SAR）。细胞周期分析表明，用1B和3AD处理后，癌细胞的百分比增加了（SUB-G1期），这也强烈抑制了黑色素瘤菌落形成。对带有A375黑色素瘤的裸鼠的体内研究表明，化合物1b以剂量依赖性方式抑制肿瘤的生长。以10 mg/kg的剂量，1B显着抑制了黑色素瘤的肿瘤生长，并且比达卡巴嗪在60 mg/kg时表现出更高的疗效。
A series of (2RS,4R)-2-arylthiazolidine-4-carboxylic acid amide (ATCAA) was synthesized. Antiproliferative activity against melanoma and prostate cancer cells compared with control cells (fibroblast and RH7777, respectively) was evaluated. Compound 3id showed the best selectivity and growth-inhibition activity against three melanoma cell lines (B16-F1, A375, and WM-164). Compounds 15b and 3ac had good selectivity and potency against four prostate cancer cell lines (DU 145, PC-3, LNCaP, and PPC-1). The structure-activity relationship (SAR) of the side chain, the thiazolidine ring, and phenyl substituents is discussed. Cell cycle analysis showed that the percentage of cancer cells undergoing apoptosis (sub-G1 phase) increased after treatment with 1b and 3ad, which also strongly inhibited melanoma colony formation. In vivo studies on nude mice bearing A375 melanoma tumors showed that compound 1b inhibited tumor growth in a dose-dependent manner. At a dose of 10 mg/kg, 1b significantly inhibited melanoma tumor growth and showed higher efficacy than did dacarbazine at 60 mg/kg.
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影响因子：
7.3
作者：
Lu Y;Li CM;Wang Z;Ross CR 2nd;Chen J;Dalton JT;Li W;Miller DD
通讯作者：
Miller DD
影响因子：
2.7
作者：
Chen, Jianjun;Wang, Zhao;Li, Wei
通讯作者：
Li, Wei
影响因子：
3
作者：
Chen, Jianping;Smith, Melissa;Higgins, Brian
通讯作者：
Higgins, Brian
影响因子：
2.7
作者：
Gududuru, V;Zeng, K;Miller, DD
通讯作者：
Miller, DD
影响因子：
254.7
作者：
Jemal, A;Tiwari, RC;Thun, MJ
通讯作者：
Thun, MJ