Pang Guang Xian, Niu Chao, Mamat Nuramina, Aisa Haji Akber
Key Laboratory of Plant Resources and Chemistry of Arid Zone, Chinese Academy of Sciences, Urumqi 830011, China; State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China; University of Chinese Academy of Sciences, 19 A Yuquan Rd, Beijing 100049, China.
Key Laboratory of Plant Resources and Chemistry of Arid Zone, Chinese Academy of Sciences, Urumqi 830011, China; State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China.
Bioorg Med Chem Lett. 2017 Jun 15;27(12):2674-2677. doi: 10.1016/j.bmcl.2017.04.039. Epub 2017 Apr 14.
A novel series of coumarin derivatives 6a-o, bearing isoxazole moieties were designed and synthesized. After that, they were evaluated for melanin synthesis in murine B16 cells and inhibitory effect on the growth of CA (Candida albicans), EC (Escherichia coli), SA (Staphylococcus aureus). It was found that eleven compounds (6b-f, 6j-o) showed a better activity on melanin synthesis than positive control (8-MOP). Among them, compounds 6d (242%) and 6f (390%), with nearly 1.6 and 2.6-fold potency compared with 8-MOP (149%) respectively, were recognized as the most promising candidate hits for further pharmacological study of anti-vitiligo. Seven halogen substituted compounds exhibited moderate antimicrobial activity against CA. It is interesting that 6e-f and 6l-m, which had two halogens on the benzene showed a comparable activity with Amphotericin B against CA. The evaluation of melanin synthesis in B16 cells and inhibitory effect on bacteria of above structurally diverse derivatives had also led to an outline of structure-activity relationship.
设计并合成了一系列带有异恶唑部分的新型香豆素衍生物6a - o。之后，对它们在小鼠B16细胞中的黑色素合成以及对白色念珠菌（CA）、大肠杆菌（EC）、金黄色葡萄球菌（SA）生长的抑制作用进行了评估。发现11种化合物（6b - f，6j - o）在黑色素合成方面表现出比阳性对照（8 - MOP）更好的活性。其中，化合物6d（242%）和6f（390%），与8 - MOP（149%）相比分别具有近1.6倍和2.6倍的效力，被认为是进一步进行抗白癜风药理学研究最有前景的候选命中物。七种卤代化合物对CA表现出中等抗菌活性。有趣的是，在苯环上有两个卤素的6e - f和6l - m对CA的活性与两性霉素B相当。对上述结构多样的衍生物在B16细胞中的黑色素合成和对细菌的抑制作用的评估也得出了构效关系的概述。
