Çiçek Serhat Sezai, Wenzel-Storjohann Arlette, Girreser Ulrich, Tasdemir Deniz
1Pharmazeutisches Institut, Abteilung Pharmazeutische Biologie, Christian-Albrechts-Universität zu Kiel, Kiel, Germany.
2GEOMAR Centre for Marine Biotechnology, Research Unit Marine Natural Products Chemistry, GEOMAR Helmholtz Centre for Ocean Research Kiel, Kiel, Germany.
Rev Bras Farmacogn. 2020;30(1):18-27. doi: 10.1007/s43450-020-00002-y. Epub 2020 Feb 21.
The oleoresin of Ducke, Fabaceae, is a traditional Brazilian remedy used for a wide range of applications. Commonly named copaiba, the oleoresin has been found to exhibit strong antimicrobial effects in our previous study, which could be attributed to some of its diterpenoid constituents. In order to find new biological activities and to eventually enhance the before observed effects, (-)-polyalthic acid () and kaurenoic acid (), together with eight prepared semi-synthetic derivatives (- and -) were evaluated for their cytotoxic, antibacterial and antifungal properties. Regarding the gram-positive bacteria and methicillin-resistant , we found that both the exocylic methylene group and the carboxyl group were crucial for the activity against these two clinically relevant bacterial strains. Investigation of the antifungal activity, in contrast, showed that the carboxyl group is unnecessary for the effect against the dermatophytes and , indicated by low micromolar IC values for both (-)-polyalthic acid diethylamide () as well as (-)-polyalthic acid methyl ester (). Apart from studying the biological activity, the structure of one semi-synthetic derivative, compound , is being reported for the first time. During the course of the structure elucidation of the new compound, we discovered inconsistencies regarding the stereochemistry of polyalthic acid and its stereoisomers, which we clarified in the present work. Graphical Abstract.
豆科植物杜克（Ducke）的油树脂是巴西一种用于多种用途的传统药物。该油树脂通常被称为古巴香脂，在我们之前的研究中发现它具有很强的抗菌作用，这可能归因于其一些二萜类成分。为了发现新的生物活性并最终增强之前观察到的效果，对（-）-多花酸（）和贝壳杉烯酸（）以及八种制备的半合成衍生物（-和-）的细胞毒性、抗菌和抗真菌特性进行了评估。关于革兰氏阳性菌和耐甲氧西林菌，我们发现环外亚甲基和羧基对于对抗这两种临床相关细菌菌株的活性至关重要。相比之下，抗真菌活性研究表明，羧基对于对抗皮肤癣菌和并非必需，（-）-多花酸二乙酰胺（）以及（-）-多花酸甲酯（）的低微摩尔IC值表明了这一点。除了研究生物活性外，首次报道了一种半合成衍生物化合物的结构。在新化合物的结构解析过程中，我们发现了多花酸及其立体异构体的立体化学存在不一致之处，我们在本工作中对此进行了澄清。图形摘要。
