Pimarane-type Diterpenes Obtained by Biotransformation: Antimicrobial Properties Against Clinically Isolated Gram-positive Multidrug-resistant Bacteria

• Published in: Phytotherapy research Vol. 27; no. 10; pp. 1502 - 1507
• Main Authors: Porto, Thiago S., Simão, Marília R., Carlos, Lucas Z., Martins, Carlos H. G., Furtado, Niege A. J. C., Said, Suraia, Arakawa, Nilton S., dos Santos, Raquel A., Veneziani, Rodrigo C. S., Ambrósio, Sérgio R.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.10.2013; Wiley Subscription Services, Inc
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - isolation & purification; Anti-Bacterial Agents - pharmacology; Antimicrobial activity; Aspergillus ochraceus; Aspergillus ochraceus - metabolism; Asteraceae - chemistry; Biotransformation; Diterpenes, Abietane - chemistry; Diterpenes, Abietane - isolation & purification; Diterpenes, Abietane - pharmacology; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; multidrug-resistant bacteria; pimarane-type diterpenes; Plant Roots - chemistry; Staphylococcus aureus; Staphylococcus aureus - drug effects; Vancomycin - pharmacology; multidrug-resistant bacteria; Aspergillus ochraceus; biotransformation; pimarane-type diterpenes; antimicrobial activity
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.4887

The present study describes the antimicrobial activity of five pimarane‐type diterpenes obtained by fungal biotransformation against several nosocomial multidrug‐resistant bacteria. Among the investigated metabolites, ent‐8(14),15‐pimaradien‐3β‐ol was the most active compound, with very promising minimal inhibitory concentration values (between 8.0 and 25.0 µg mL−1). Time‐kill assays using this metabolite against Staphylococcus aureus (HCRP180) revealed that this compound exerted its bactericidal effect within 24 h at all the evaluated concentrations (8.0, 16.0, and 24.0 µg mL−1). When this metabolite was associated with vancomycin at their minimal bactericidal concentration values, the resulting combination was able to drastically reduce the number of viable strains of S. aureus within the first 6 h, compared with these chemicals alone. The checkerboard assays conducted against this microorganism did not evidence any synergistic effects when this same combination was employed. In conclusion, our results point out that ent‐8(14),15‐pimaradien‐3β‐ol is an important metabolite in the search for new effective antimicrobial agents. Copyright © 2012 John Wiley & Sons, Ltd.