Anna Laís Pfeifer Barbosa1, Arlette Wenzel-Storjohann2, José Diomedes Barbosa3, Christian Zidorn4, Christian Peifer5, Deniz Tasdemir6, Serhat Sezai Çiçek7. 1. Pharmazeutisches Institut, Abteilung Pharmazeutische Biologie, Christian-Albrechts-Universität zu Kiel, Gutenbergstraße 76, 24118 Kiel, Germany; Pharmazeutisches Institut, Abteilung Pharmazeutische und Medizinische Chemie, Christian-Albrechts-Universität zu Kiel, Gutenbergstraße 76, 24118 Kiel, Germany. 2. GEOMAR Centre for Marine Biotechnology, Research Unit Marine Natural Products Chemistry, GEOMAR Helmholtz Centre for Ocean Research Kiel, Am Kiel-Kanal 44, 24106 Kiel, Germany. Electronic address: awenzel-storjohann@geomar.de. 3. Central de Diagnóstico Veterinário, Faculdade de Medicina Veterinária, Universidade Federal do Pará, Campus Castanhal, Rua Maximino Porpino da Silva, 1000, 68710-080 Castanhal, PA, Brazil. Electronic address: diomedes@ufpa.br. 4. Pharmazeutisches Institut, Abteilung Pharmazeutische Biologie, Christian-Albrechts-Universität zu Kiel, Gutenbergstraße 76, 24118 Kiel, Germany. Electronic address: czidorn@pharmazie.uni-kiel.de. 5. Pharmazeutisches Institut, Abteilung Pharmazeutische und Medizinische Chemie, Christian-Albrechts-Universität zu Kiel, Gutenbergstraße 76, 24118 Kiel, Germany. Electronic address: cpeifer@pharmazie.uni-kiel.de. 6. GEOMAR Centre for Marine Biotechnology, Research Unit Marine Natural Products Chemistry, GEOMAR Helmholtz Centre for Ocean Research Kiel, Am Kiel-Kanal 44, 24106 Kiel, Germany; Christian-Albrechts-Universität zu Kiel, 24118 Kiel, Germany. Electronic address: dtasdemir@geomar.de. 7. Pharmazeutisches Institut, Abteilung Pharmazeutische Biologie, Christian-Albrechts-Universität zu Kiel, Gutenbergstraße 76, 24118 Kiel, Germany. Electronic address: scicek@pharmazie.uni-kiel.de.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: The oleoresin of Brazilian Copaifera reticulata is a traditional remedy used for the treatment of skin and urinary tract infections, respiratory diseases, rheumatism, ulcer and tumours; thus, playing an important role in the primary health care of the indigenous population. AIM: As most previous pharmacological tests used the crude oleoresin and only a few studies so far dealt with enriched fractions or pure chemically defined compounds, the aim of this study was to systematically evaluate the antimicrobial and cytotoxic properties of the Copaifera reticulata oleoresin and to assign traditional uses to specific secondary metabolites. MATERIALS AND METHODS: The oleoresin, as well as its neutral and acidic fractions were tested for their activity against six cancer cell lines, two clinically relevant bacterial strains, and two dermatophytes. Both fractions were analysed by GC-MS and UHPLC-ELSD, respectively. The antibacterial acidic phase was further fractionated by preparative chromatography to purify and characterize the compounds responsible for the observed pharmacological effect. RESULTS: Whereas no cytotoxic activity was detected, the crude oleoresin and its acidic fraction showed antibacterial activity against gram-positive bacteria Enterococcus faecium (IC50 values 4.2 and 4.8 µg/mL, respectively) and methicillin-resistant Staphylococcus aureus (MRSA, IC50 values 5.3 and 7.2 µg/mL, respectively). Purification of the acidic fraction of the C. reticulata oleoresin yielded two dicarboxylic diterpene acids and the four main diterpene acids, comprising three different diterpene scaffolds. Interestingly, the activity was not restricted to a particular diterpene-type but rather depended on the compounds' lipophilicity, with the most active constituent showing IC50 values of 1.6 (E. faecium) and 2.5 µg/mL (MRSA), respectively. Furthermore, ent-polyalthic acid, the major diterpenoid, was significantly active against dermatophytes with IC50 values of 6.8 µg/mL (Trichophyton rubrum) and 4.3 µg/mL against (T. mentagrophytes). CONCLUSION: The present study proved the antimicrobial effects of the C. reticulata oleoresin and its diterpenoid constituents, confirming its wide use in folk medicine for the treatment of skin and urinary tract infections. The inhibitory activity of copaiba diterpenoids against dermatophytic fungi as well as the gram-positive bacteria E. faecium and MRSA is being reported for the first time, providing potential lead structures for the treatment of these clinically relevant bacterial strains.
ETHNOPHARMACOLOGICAL RELEVANCE: The oleoresin of Brazilian Copaifera reticulata is a traditional remedy used for the treatment of skin and urinary tract infections, respiratory diseases, rheumatism, ulcer and tumours; thus, playing an important role in the primary health care of the indigenous population. AIM: As most previous pharmacological tests used the crude oleoresin and only a few studies so far dealt with enriched fractions or pure chemically defined compounds, the aim of this study was to systematically evaluate the antimicrobial and cytotoxic properties of the Copaifera reticulata oleoresin and to assign traditional uses to specific secondary metabolites. MATERIALS AND METHODS: The oleoresin, as well as its neutral and acidic fractions were tested for their activity against six cancer cell lines, two clinically relevant bacterial strains, and two dermatophytes. Both fractions were analysed by GC-MS and UHPLC-ELSD, respectively. The antibacterial acidic phase was further fractionated by preparative chromatography to purify and characterize the compounds responsible for the observed pharmacological effect. RESULTS: Whereas no cytotoxic activity was detected, the crude oleoresin and its acidic fraction showed antibacterial activity against gram-positive bacteria Enterococcus faecium (IC50 values 4.2 and 4.8 µg/mL, respectively) and methicillin-resistant Staphylococcus aureus (MRSA, IC50 values 5.3 and 7.2 µg/mL, respectively). Purification of the acidic fraction of the C. reticulata oleoresin yielded two dicarboxylic diterpene acids and the four main diterpene acids, comprising three different diterpene scaffolds. Interestingly, the activity was not restricted to a particular diterpene-type but rather depended on the compounds' lipophilicity, with the most active constituent showing IC50 values of 1.6 (E. faecium) and 2.5 µg/mL (MRSA), respectively. Furthermore, ent-polyalthic acid, the major diterpenoid, was significantly active against dermatophytes with IC50 values of 6.8 µg/mL (Trichophyton rubrum) and 4.3 µg/mL against (T. mentagrophytes). CONCLUSION: The present study proved the antimicrobial effects of the C. reticulata oleoresin and its diterpenoid constituents, confirming its wide use in folk medicine for the treatment of skin and urinary tract infections. The inhibitory activity of copaibaditerpenoids against dermatophytic fungi as well as the gram-positive bacteria E. faecium and MRSA is being reported for the first time, providing potential lead structures for the treatment of these clinically relevant bacterial strains.
Authors: Caroline Utermann; Vivien A Echelmeyer; Ernest Oppong-Danquah; Martina Blümel; Deniz Tasdemir Journal: Mar Drugs Date: 2020-12-24 Impact factor: 5.118
Authors: François Chassagne; Tharanga Samarakoon; Gina Porras; James T Lyles; Micah Dettweiler; Lewis Marquez; Akram M Salam; Sarah Shabih; Darya Raschid Farrokhi; Cassandra L Quave Journal: Front Pharmacol Date: 2021-01-08 Impact factor: 5.810
Authors: João V C Batista; Annekathrin Uecker; Carla Holandino; Fabio Boylan; Jakob Maier; Jörg Huwyler; Stephan Baumgartner Journal: Front Pharmacol Date: 2022-06-03 Impact factor: 5.988
Authors: Floriana Cappiello; Maria Rosa Loffredo; Cristina Del Plato; Silvia Cammarone; Bruno Casciaro; Deborah Quaglio; Maria Luisa Mangoni; Bruno Botta; Francesca Ghirga Journal: Antibiotics (Basel) Date: 2020-06-13