Design, synthesis, and biological evaluation of N-acetyl-S-(p-chlorophenylcarbamoyl)cysteine and its analogs as a novel class of anticancer agents.
Design, synthesis, and biological evaluation of N-acetyl-S-(p-chlorophenylcarbamoyl)cysteine and its analogs as a novel class of anticancer agents.
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DOI：
10.1016/j.bmc.2010.11.026
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发表时间：
2011-01-01
影响因子：
3.5
通讯作者：
Guan, Xiangming
中科院分区：
文献类型：
--
作者：
Chen, Wei;Seefeldt, Teresa;Young, Alan;Zhang, Xiaoying;Guan, Xiangming
N-乙酰基-S-（对氯苯氨甲酰基）半胱氨酸（NACC）被鉴定为硫柳汞的代谢产物。在临床前研究中，已证明Sudaluur对实体瘤具有广泛的活性，但由于其高蛋白结合相关的不良反应，其临床反应令人失望。NACC表现出低蛋白结合和优异的抗硫敏感的人结肠癌细胞系的活性。在这项研究中，NACC类似物的合成和评估与四个人癌细胞系。NACC类似物中的两种对两种人黑素瘤细胞系显示出优异的活性，而NACC仍然是该系列中最有效的。这三种化合物都比达卡巴嗪更有效，达卡巴嗪广泛用于治疗黑色素瘤。NACC可诱导细胞凋亡而不影响细胞周期。此外，NACC对猴肾细胞表现出低毒性。NACC及其类似物具有选择性的抗癌活性、低毒性、未知但独特的抗癌机制以及易于合成等优点，是一种很有前途的抗癌药物。
N-Acetyl-S-(p-chlorophenylcarbamoyl)cysteine (NACC) was identified as a metabolite of sulofenur. Sulofenur was demonstrated to have broad activity against solid tumors in preclinical studies but exhibited disappointing clinical responses due to its high protein binding related adverse effects. NACC exhibited low protein binding and excellent activity against a sulofenur sensitive human colon cancer cell line. In this study, analogs of NACC were synthesized and evaluated with four human cancer cell lines. Two of the NACC analogs showed excellent activity against two human melanoma cell lines, while NACC remains the most potent of the series. All three compounds were more potent than dacarbazine, which is used extensively in treating melanoma. NACC was shown to induce apoptosis without affecting the cell cycle. Further, NACC exhibited low toxicity against monkey kidney cells. The selective anticancer activity, low toxicity, an unknown yet but unique anticancer mechanism and ready obtainability through synthesis make NACC and its analogs promising anticancer agents.
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皮肤黑色素瘤中与健康相关的生活质量的系统评价。
DOI：
10.1093/annonc/mdp255
发表时间：
2009-08
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Cornish D;Holterhues C;van de Poll-Franse LV;Coebergh JW;Nijsten T
通讯作者：
Nijsten T
影响因子：
3.9
作者：
Guan, XM;Hoffman, BN;Pellegrini, J
通讯作者：
Pellegrini, J
影响因子：
7.3
作者：
MOHAMADI, F;SPEES, MM;GRINDEY, GB
通讯作者：
GRINDEY, GB
DOI：
10.1093/annonc/mdp257
发表时间：
2009-08
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Testori A;Rutkowski P;Marsden J;Bastholt L;Chiarion-Sileni V;Hauschild A;Eggermont AM
通讯作者：
Eggermont AM
影响因子：
9.7
作者：
PHELPS, PC;JAIN, PT;TRUMP, BF
通讯作者：
TRUMP, BF