基于结构的新肉桂酸衍生物酪氨酸酶抑制剂药物设计

IF 0.7 4区化学 Q4 CHEMISTRY, ORGANIC

Letters in Organic Chemistry Pub Date : 2024-01-26 DOI:10.2174/0115701786263337231227113513

Fayezeh Yousefnejad, Mohammad Hossein Sayahi, Ali Mazzam, Fatemeh Gholami, Nader Tanideh, Cambyz Irajie, Helia Tayebi, Fatemeh Rasekh, Bagher Larijani, Maliheh Barazandeh Tehrani, Mohammad Mahdavi, Aida Iraji

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引用次数: 0

摘要

:酪氨酸酶是导致色素沉着症的关键酶，抑制酪氨酸酶是治疗色素沉着症的既定策略。本研究设计并合成了肉桂酸衍生物。所有合成的化合物都通过红外光谱、1 HNMR、13CNMR 和 CNH 分析进行了确认。测定了所有衍生物对酪氨酸酶的抑制效力，结果表明含有对位氯分子的 5m 的 IC50 值为 77.62 µmol/L。酶动力学研究分析表明，5m 是一种非竞争性抑制剂。针对酪氨酸酶的硅学研究预测了口袋中的可能结合模式，即 5m 在结合位点内与两种铜辅助因子形成关键的相互作用。本研究揭示了芳基取代肉桂酸作为脱色剂在各种化妆品配方中的应用潜力。

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Structure-based Drug Design of New Cinnamic Acid Derivatives as Tyrosinase Inhibitors

: Tyrosinase is a critical enzyme responsible for pigmentation disorders, and tyrosinase inhibition is an established strategy to treat hyperpigmentation. In the current study, cinnamic acidbased derivatives were designed and synthesized. All synthesized compounds were confirmed using IR, 1 HNMR, 13CNMR, and CNH analysis. The inhibitory potencies of all derivatives against tyrosinase were determined, and it was shown that 5m bearing para-chloro moiety exhibits an IC50 value of 77.62 µmol/L. Analysis of enzyme kinetic studies revealed that 5m is an uncompetitive inhibitor. In silico studies against tyrosinase predicted possible binding mode in the pocket such that 5m formed critical interactions with both Cu co-factors within the binding site. This study presents the potential of aryl-substituted cinnamic acids that can benefit various cosmetic formulations as depigmentation agents.

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来源期刊

Letters in Organic Chemistry 化学-有机化学

CiteScore

1.30

自引率

12.50%

发文量

135

审稿时长

7 months

期刊介绍： Aims & Scope Letters in Organic Chemistry publishes original letters (short articles), research articles, mini-reviews and thematic issues based on mini-reviews and short articles, in all areas of organic chemistry including synthesis, bioorganic, medicinal, natural products, organometallic, supramolecular, molecular recognition and physical organic chemistry. The emphasis is to publish quality papers rapidly by taking full advantage of latest technology for both submission and review of the manuscripts. The journal is an essential reading for all organic chemists belonging to both academia and industry.