Maciel Olívia Maria Campanini, Tavares Renata Spagolla Napoleão, Caluz Daniela Ricardo Engracia, Gaspar Lorena Rigo, Debonsi Hosana Maria
Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto - University of Sao Paulo, Ribeirao Preto, Brazil.
Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences of Ribeirão Preto - University of Sao Paulo, Ribeirao Preto, Brazil.
J Photochem Photobiol B. 2018 Jan;178:316-322. doi: 10.1016/j.jphotobiol.2017.11.018. Epub 2017 Nov 21.
Natural products, or secondary metabolites, obtained from fungal species associated with marine algae have been widely used in sunscreens due to their antioxidant activity and protective potential against solar radiation. The endophytic fungus isolated from Bostrychia radicans algae collected in the Rio Escuro mangrove, São Paulo State, Brazil, Annulohypoxylon stygium (Xylariaceae family) was studied to evaluate the photoprotective potential of its metabolites. The Annulohypoxylon genus can produce secondary metabolites with interesting cytotoxic, antibacterial and antioxidant properties and was never isolated before from a marine alga or had its metabolites studied for UV protection. The fungal culture (code As) extracted with dichloromethane: methanol (2:1) yielded 9 fractions (Asa to Asi) which were submitted to different chromatographic methodologies to obtain pure compounds, and to spectroscopic methodologies to elucidate their structures. Also, a screening was conducted to evaluate the qualitative production of the metabolites, besides the absorption in the UVA/UVB range, their photostability and phototoxicity potential using the 3T3 NRU phototoxicity test (OECD TG 432). This study led to the isolation of a novel compound, 3-benzylidene-2-methylhexahydropyrrolo [1,2-α] pyrazine-1,4-dione (1), from fractions Ase3 and Asf3; Ase1 was identified as 1-(1,3-Benzodioxol-5-yl)-1,2-propanediol (2), two metabolites were isolated as diastereomers (1S,2R)-1-phenyl-1,2-propanediol (3) from Asd2 and (1R,2R)-1-phenyl-1,2-propanediol (4) from Asd3, and Ase1 and 1,3-benzodioxole-5-methanol (5) from Asc1. The results obtained showed a great potential source of new molecules to be used as UVB filters in sunscreens, since substances 1-2 presented UVB absorption, had no phototoxic potential and were considered photostable. In conclusion, these compounds can be considered as a potential new class of molecules for photoprotection, since their photosafety and non-cytotoxicity were predicted using in vitro methods for topical use. Meanwhile, further efficacy assays shall be conducted for the establishment of their Sun Protection Factor (SPF). Also, this work provided new information concerning the metabolic profile of A. stygium, since it was possible to obtain two enantiomer compounds (3) and (4). One of them belonged to the same skeleton, but with a methylenedioxy moiety, showing the richest enzymatic pattern for this microorganism.
从与海藻相关的真菌物种中获得的天然产物或次生代谢物，因其抗氧化活性和对太阳辐射的防护潜力，已被广泛应用于防晒霜中。对从巴西圣保罗州埃斯库罗河红树林采集的辐射波氏藻中分离出的内生真菌——暗褐环脐菇（炭角菌科）进行了研究，以评估其代谢物的光保护潜力。环脐菇属能产生具有有趣细胞毒性、抗菌和抗氧化特性的次生代谢物，此前从未从海藻中分离得到过该属真菌，也未对其代谢物进行过紫外线防护方面的研究。用二氯甲烷：甲醇（2:1）萃取的真菌培养物（编号为As）得到了9个馏分（从Asa到Asi），这些馏分经过不同的色谱方法以获得纯化合物，并经过光谱方法以阐明其结构。此外，还进行了一项筛选，除了评估代谢物在UVA/UVB范围内的吸收、光稳定性和光毒性潜力外，还使用3T3 NRU光毒性试验（经合组织TG 432）评估代谢物的定性产生情况。这项研究从馏分Ase3和Asf3中分离出一种新型化合物，3-亚苄基-2-甲基六氢吡咯并[1,2-α]吡嗪-1,4-二酮（1）；Ase1被鉴定为1-(1,3-苯并二氧杂环戊烯-5-基)-1,2-丙二醇（2），从Asd2中分离出两种非对映异构体代谢物(1S,2R)-1-苯基-1,2-丙二醇（3），从Asd3中分离出(1R,2R)-1-苯基-1,2-丙二醇（4），从Asc1中分离出Ase1和1,3-苯并二氧杂环戊烯-5-甲醇（5）。所得结果表明，这些物质是用作防晒霜中UVB滤光剂的新分子的巨大潜在来源，因为物质1-2具有UVB吸收，无光毒性潜力且被认为具有光稳定性。总之，这些化合物可被视为一类潜在的新型光保护分子，因为通过体外局部使用方法预测了它们的光安全性和无细胞毒性。同时，应进行进一步的功效测定以确定它们的防晒系数（SPF）。此外，这项工作提供了关于暗褐环脐菇代谢谱的新信息，因为有可能获得两种对映体化合物（3）和（4）。其中一种属于相同骨架，但带有亚甲二氧基部分，显示出该微生物最丰富的酶模式。
