Antimicrobial Potential of Natural and Semi-Synthetic ent-Kaurane and ent-Pimarane Diterpenes against Clinically Isolated Gram-Positive Multidrug-Resistant Bacteria

• Published in: Journal of the Brazilian Chemical Society Vol. 30; no. 2; pp. 333 - 341
• Main Authors: Soares, Ana Carolina, Matos, Priscilla, da Silva, Karime, Martins, Carlos, Veneziani, Rodrigo, Ambrósio, Sérgio, Dias, Herbert, dos Santos, Raquel, Heleno, Vladimir
• Format: Journal Article
• Language: English
• Published: Sociedade Brasileira de Química 01-02-2019
• Subjects: CHEMISTRY, MULTIDISCIPLINARY; multidrug-resistant bacteria; pimarane diterpenes; antimicrobial activity; kaurane diterpenes; Staphylococcus aureus
• ISSN: 0103-5053; 1678-4790; 1678-4790
• DOI: 10.21577/0103-5053.20180182

In this work, a search for antimicrobial agents against multi-drug resistant (MDR) bacteria was undertaken. It involved two natural diterpenes of different basic skeletons, named ent-kaurenoic acid and ent-pimaradienoic acid, that were used as precursors to access 28 semi-synthetic derivatives that were also submitted to biological assays. All 30 substances were assayed against a set of seven clinically isolated MDR bacteria, including three Staphylococcus aureus strains. Results classified both natural compounds as promising bactericidal antimicrobial agents against these MDR bacteria, especially for their performance in time-kill curve assay, improving on the positive control vancomycin. Moreover, di-hydro ent-pimaradienoic acid, obtained as one of the derivatives, also displayed promising minimum inhibitory concentration (MIC) values against the microorganism set, proving optimum activity against S. aureus strains. Thereby, this work also yielded a promising semi-synthetic bacteriostatic antimicrobial agent against MDR S. aureus. Furthermore, the study was carried out with 30 structures in order to verify the veracity and scope of Urzúa’s hypothesis about the structure-activity relationship between diterpenes and antimicrobial action. Our results are 93% in agreement with this hypothesis.