摘要
许多美白产品及皮肤色素异常的治疗药物都含有酪氨酸酶抑制剂,其主要功能是减少皮肤黑色素的生成,目前市面上黑色素抑制剂均有一定的副作用或其美白效能不如理想,因此近10年来研发了许多高效能的酪氨酸酶抑制剂,但对其毒性的研究则寥寥可数。本研究采用以定量构效关系模型(QSAR)为主要原理的计算机毒性研究软件Toxtree对643个从文献及BindingDB数据库中取得的酪氨酸酶抑制剂进行皮肤毒性研究,发现其中约一半的带有刺激性、腐蚀性或致癌性。本研究亦对这643个抑制剂进行柔性分子对接,其目标为能促成黑色素生成的腺苷酸环化酶(adenylyl cyclase,AC)。通过分析这643个抑制剂对酪氨酸酶的抑制常数(IC_(50))、脂水分配系数、计算机毒理预测进行及对AC的分子对接结果,认为化合物ChEMBL,228162、228164和491410有最高的药物潜在价值。
Many skin-whitening products used to reduce the formation of skin melanin contain tyrosinase inhibitors, whose side effects and effectiveness are considered to be improved. Over the past decade, various compounds with advanced tyrosinase inhibition activity have been produced; however, most of their toxicities are unknown. This study predicts the skin toxicity of 643 tyrosinase inhibitors found in Binding Database and literature by the QSAR based software, Toxtree. Results indicate that half of them are irritant, corrosive or carcinogenic. This study also performed complete protein flexible docking calculations of the 643 tyrosinase inhibitors to another melanogensis related enzyme, adenylyl cyclase. Analysis of their tyrosinase inhibition constant （IC50）, octanol-water partition coefficient, skin toxicity prediction and docking simulation conclude that compound ChEMBL 228162, 228164 and 491410 are the best drug candidates for further investigations.
出处
《计算机与应用化学》
CAS
CSCD
北大核心
2012年第10期1231-1236,共6页
Computers and Applied Chemistry
基金
澳门科学技术发展基金资助研究项目(004/2010/A)
科技
关键词
计算机毒性预测
酪氨酸酶抑制剂
美白
In silico toxicity prediction, tyrosinase inhibitor, skin-whitening processes
