Biological Activities of Two Major Copaiba Diterpenoids and Their Semi-synthetic Derivatives

Serhat Sezai Çiçek,Arlette Wenzel-Storjohann,Ulrich Girreser,Deniz Tasdemir

doi:10.1007/s43450-020-00002-y

Serhat Sezai Çiçek, Arlette Wenzel-Storjohann + Show 2 more

Open Access

https://doi.org/10.1007/s43450-020-00002-y

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Abstract

The oleoresin of Copaifera reticulata 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 (1) and kaurenoic acid (2), together with eight prepared semi-synthetic derivatives (1a–1c and 2a–2e) were evaluated for their cytotoxic, antibacterial and antifungal properties. Regarding the gram-positive bacteria Enterococcus faecium and methicillin-resistant Staphylococcus aureus, 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 Trichophyton rubrum and Cryptococcus neoformans, indicated by low micromolar IC50 values for both (−)-polyalthic acid diethylamide (1a) as well as (−)-polyalthic acid methyl ester (1b). Apart from studying the biological activity, the structure of one semi-synthetic derivative, compound 1c, 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 .

Highlights

Copaiba, or copaiba oil, is the name of an oleoresin obtained from selected species of the genus Copaifera, Fabaceae (Leandro et al 2012)
Copaiba consists of sesquiterpenes and diterpenes, the latter usually being present as diterpene acids (Leandro et al 2012)
Βbisabolene has been identified as the major sesquiterpene of Copaifera reticulata Ducke collected in the Pará region (Pfeifer Barbosa et al 2019)

Summary

Introduction

Copaiba oil, is the name of an oleoresin obtained from selected species of the genus Copaifera, Fabaceae (Leandro et al 2012). Antidermatophytic activity against two Trichopyhton species was detected for (−)-polyalthic acid (1), the major diterpenoid in the Copaifera reticulata oleoresin, along with weak [(−)-polyalthic acid, 1] to moderate (kaurenoic acid, 2) cytotoxic effects against six cancer cell lines. These findings prompted us to prepare semi-synthetic derivatives of both compounds in an attempt to enhance their antimicrobial and cytotoxic properties and to get more insights into their structure-activity-relationships (SAR). Additional screenings were performed to discover new lead compounds against both human and plant pathogens

Materials and Methods

Results and Discussion

Conclusion