Alexandrino Thaís Dolfini, de Medeiros Tiago Daniel Madureira, Ruiz Ana Lúcia Tasca Gois, Favaro Denize Cristina, Pastore Gláucia Maria, Bicas Juliano Lemos
School of Food Engineering, Department of Food Science, University of Campinas, Campinas, Brazil.
Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, Brazil.
Chirality. 2022 Jun;34(6):887-893. doi: 10.1002/chir.23439. Epub 2022 Apr 14.
Limonene-1,2-diol is a limonene oxygenated metabolite that possesses eight different stereoisomers, which could result in different biological properties. Nonetheless, the relation between its spatial configuration and biological function is still little explored. The present study aimed to perform the stereoisomers identification using nuclear magnetic resonance (NMR) investigation of the limonene-1,2-diol produced via R-(+)- and S-(-)-limonene biotransformation by Colletotrichum nymphaeae and S-(-)-limonene biotransformation by Fusarium oxysporum 152B. Besides, in vitro antiproliferative activity was evaluated against human tumor and nontumor cell lines. The NMR analysis showed that R-(+)-limonene biotransformation afforded exclusively (+)-(1S,2S,4R-limonene-1,2-diol), whereas S-(-)-limonene biotransformation afforded exclusively (-)-(1R,2R,4S-limonene-1,2-diol) independent on the fungi used. Despite no significant cytostatic effects, a possible influence of stereogenic center on the antiproliferative activity of these limonene biotransformation products was evidenced. Moreover, the lack of in vitro antiproliferative effect of limonene-1,2-diol against nontumor cells suggested a safe dose range for further in vivo evaluations, including food applications.
柠檬烯 -1,2 -二醇是一种柠檬烯氧化代谢产物，具有八种不同的立体异构体，这可能导致不同的生物学特性。尽管如此，其空间构型与生物学功能之间的关系仍鲜少被探索。本研究旨在通过核磁共振（NMR）对经由睡莲炭疽菌对R-(+)-柠檬烯和S-(-)-柠檬烯的生物转化以及尖孢镰刀菌152B对S-(-)-柠檬烯的生物转化所产生的柠檬烯 -1,2 -二醇进行立体异构体鉴定。此外，还评估了其对人肿瘤和非肿瘤细胞系的体外抗增殖活性。核磁共振分析表明，R-(+)-柠檬烯的生物转化仅产生(+)-(1S,2S,4R)-柠檬烯 -1,2 -二醇，而S-(-)-柠檬烯的生物转化仅产生(-)-(1R,2R,4S)-柠檬烯 -1,2 -二醇，与所使用的真菌无关。尽管没有显著的细胞抑制作用，但已证明手性中心对这些柠檬烯生物转化产物的抗增殖活性可能有影响。此外，柠檬烯 -1,2 -二醇对非肿瘤细胞缺乏体外抗增殖作用，这为包括食品应用在内的进一步体内评估提示了一个安全剂量范围。
