兼具抗氧化能力的新型二氢吡啶类防晒剂的筛选

Screening of a novel dihydropyridine sunscreen with antioxidant capacity

关键词:  二氢吡啶  防晒剂  抗氧化剂  苯酚  基于片段的药物设计

Key words:  dihydropyridine  antioxidant  sunscreen  phenol  fragment-based drug design

摘要:

目的：构建并筛选一类兼具较强抗氧化能力和防晒能力的新型二氢吡啶类化合物。方法：通过基于片段药物设计策略,以二氢吡啶结构为母核,设计并合成结构类型多样的全新化合物,通过核磁、质谱确证结构；用DPPH、ABTS、FRAP法测试该系列化合物的抗氧化能力,通过紫外分光光度法测试紫外吸收能力；筛选兼具较强抗氧化能力及防晒能力的化合物并进行构效关系分析。结果：成功构建了全新结构的二氢吡啶类化合物29个并完成了结构确证,筛选出了抗氧化能力较好的化合物ZA01、ZA31、ZC01和ZC32,紫外吸收能力强的化合物ZA01、ZA31、ZC01、ZC11和ZC13,其中ZA01、ZA31和ZC01兼具较强的抗氧化能力及紫外吸收能力。结论：在二氢吡啶母核4位引入3-甲氧基-4-羟基苯基,能明显提升抗氧化能力和紫外线吸收能力,若在4位引入对硝基苯基,则能得到广谱的紫外吸收能力,若引入叔丁基,则能明显提升在UVB段的吸收能力,以ZA01、ZA31和ZC01为代表的二氢吡啶类化合物有望进一步开发为兼具抗氧化能力的新型防晒剂。

Abstract:

Objective Design and screening of a novel class of dihydropyridine compounds with both potent antioxidant and sunscreen properties. Methods Utilizing a fragment-based drug design strategy, a series of novel compounds based on the dihydropyridine structure were designed and synthesized, and their structures were subsequently verified by nuclear magnetic resonance and high-resolution mass spectrometry. The DPPH, ABTS and FRAP methods were used to assess the antioxidant capacity of this series of compounds, while UV spectrophotometry was used to evaluate their UV absorption capability. The aim was to identify compounds with both potent antioxidant and sunscreen properties and to analyze the structure-activity relationships. Results A total of 29 novel dihydropyridine compounds were successfully constructed and their structures were confirmed. Compounds ZA01, ZA31, ZC01, and ZC32 with excellent antioxidant capacity and compounds ZA01, ZA31, ZC01, ZC11, and ZC13 with strong ultraviolet absorption capacity were identified. Among them, ZA01, ZA31, and ZC01exhibits both potent antioxidant and sunscreen properties. Conclusion Introduction of 3-methoxy-4-hydroxyphenyl at position 4 of the dihydropyridine nucleus can significantly enhance antioxidant and UV absorption capabilities. Introduction of p-nitrophenyl at position 4 can result in broad-spectrum UV absorption capabilities, while introduction of tert-butyl can significantly improve absorption capabilities in the UVB range. Compounds represented by ZA01, ZA31, and ZC01 have the potential to be further developed into highly effective sunscreens or antioxidants.