Antitubercular Activity Increase in Labdane Diterpenes from Copaifera Oleoresin through Structural Modification

• Autor(a) principal: Silva,Aline N.
• Data de Publicação: 2017
• Outros Autores: Soares,Ana Carolina F., Cabral,Mirela M. W., Andrade,Alex R. P. de, Silva,Marilza B. M. da, Martins,Carlos H. G., Veneziani,Rodrigo C. S., Ambrósio,Sérgio R., Bastos,Jairo K., Heleno,Vladimir C. G.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of the Brazilian Chemical Society (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532017000601106
• topic: Copaifera oilresin; labdane diterpenes; structural modification; antitubercular activity; Mycobacterium tuberculosis

The labdane diterpenes copalic acid, 3β-acetoxy-copalic acid, 3β-hydroxy-copalic acid and ent-agathic acid were isolated from Copaifera langsdorffii oleoresin. These four compounds were submitted to structural modifications by reduction with hydrogen/palladium, esterification with diazomethane, esterification with methanol/sulfuric acid and conversion into sodium salt, furnishing 15 compounds. All compounds were assayed in vitro against Mycobacterium tuberculosis (H37Rv, ATCC 27294). The four compounds displayed minimum inhibitory concentration (MIC) value of 125 µg mL-1, and were not considered active. A methylated derivative of compound 3β-hydroxy-copalic acid, and a sodium salt of copalic acid displayed MIC values of 25 µg mL-1 (71.7 µM) and 6.25 µg mL-1 (19.2 µM), respectively. The sodium salt of copalic acid stood out by displaying similar activity in comparison with streptomycin (MIC 6.25 µg mL-1) and a better activity compared to µM value of pyrazinamide (MIC 3.12 µg mL-1; 25.34 µM). Therefore, the methylated derivative of compound 3β-hydroxy-copalic acid and the sodium salt of copalic acid should be considered for further studies.