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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 whitening products and skin pigmentation therapy include tyrosinase inhibitors, its main function is to reduce the formation of skin melanin, melanin inhibitors currently on the market have some side effects or whitening efficiency is less than ideal, so nearly 10 In recent years, many high-performance tyrosinase inhibitors have been developed, but few studies have reported on their toxicity. In this study, Toxtree, a computer toxicology software based on quantitative structure-activity relationship model (QSAR), was used to study the skin toxicity of 643 tyrosinase inhibitors obtained from the literature and BindingDB database and found that about half Irritant, corrosive or carcinogenic. In this study, flexible molecular docking was also performed on these 643 inhibitors, targeting adenylyl cyclase (AC) that contributes to melanin production. The compounds ChEMBL, 228162, 228164 and 491410 were considered to have the inhibitory constant of tyrosinase (IC 50), the lipid-water partition coefficient, the prediction of computer toxicology and the molecular docking results to AC by analyzing these 643 inhibitors. The highest drug potential value.