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Potent anti-melanogenic activity and favorable toxicity profile of selected 4-phenyl hydroxycoumarins in the zebrafish model and the computational molecular modeling studies
Bioorganic & Medicinal Chemistry ( IF 3.3 ) Pub Date : 2017-09-18 , DOI: 10.1016/j.bmc.2017.09.021
Jovana B. Veselinović , Aleksandar M. Veselinović , Tatjana Ilic-Tomic , Reeta Davis , Kevin O'Connor , Aleksandar Pavic , Jasmina Nikodinovic-Runic

7-Hydroxy-4-phenylcoumarin (7C) and 5,7-dihydroxy-4-phenylcoumarin (5,7C) have been evaluated as potential anti-melanogenic agents in the zebrafish (Danio rerio) model in comparison to commercially utilized depigmenting agents hydroquinone and kojic acid. 7C and 5,7C decreased the body pigmentation at 5 µg/mL, while did not affect the embryos development and survival at doses ≤50 µg/mL and ≤25 µg/mL. Unlike hydroquinone and kojic acid, 4-phenyl hydroxycoumarins were no melanocytotoxic, showed no cardiotoxic side effects, neither caused neutropenia in zebrafish embryos, suggesting these compounds may present novel skin-whitening agents with improved pharmacological properties. Inhibition of tyrosinase was identified as the possible mode of anti-melanogenic action. Molecular docking studies using the homology model of human tyrosinase as well as adenylate cyclase revealed excellent correlation with experimentally obtained results.



中文翻译:

选定的4-苯基羟基香豆素在斑马鱼模型中的强抗黑素活性和有利的毒性特征以及计算分子模型研究

7-羟基-4-苯基香豆素(7C)和5,7-二羟基-4-苯基香豆素(5,7C)已被评估为斑马鱼中潜在的抗黑色素生成剂(Danio rerio与商业上使用的脱色剂氢醌和曲酸相比)。7C和5,7C在5 µg / mL时降低了人体色素沉着,而在≤50µg / mL和≤25µg / mL的剂量下不影响胚胎的发育和存活。与对苯二酚和曲酸不同,4-苯基羟基香豆素没有黑素细胞毒性,没有心脏毒性副作用,也没有引起斑马鱼胚胎中性白细胞减少症,这表明这些化合物可以提供具有改善药理特性的新型皮肤增白剂。酪氨酸酶的抑制被确定为抗黑色素作用的可能模式。使用人酪氨酸酶和腺苷酸环化酶的同源性模型进行的分子对接研究显示出与实验获得的结果极好的相关性。

更新日期:2017-09-18
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