1. Variability of the antibacterial potential among analogue diterpenes against Gram-positive bacteria: considerations on the structure-activity relationship
- Author
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Soares, Ana Carolina Ferreira, Matos, Priscilla Mendonca, Dias, Herbert, Jr., Aguiar, Gabriela de Paula, dos Santos, Eliene Silverio, Martins, Carlos Henrique Gomes, Veneziani, Rodrigo Cassio Sola, Ambrosio, Sergio Ricardo, and Heleno, Vladimir Constantino Gomes
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Bacteria -- Health aspects ,Antibacterial agents -- Health aspects ,Chemistry ,World Health Organization - Abstract
The search for new antibacterial agents and a better comprehension of substances with antimicrobial behavior is mandatory nowadays due to the serious public health problem of infection diseases. In the present work, 30 diterpenes were studied, with 2 natural derivatives, named ent-16-kauren-19-oic acid and ent-pimara-8(14), 15-dien-19-oic acid, and 28 semisynthetic derivatives. The natural diterpenes were isolated from Mikania glomerata and Viguiera arenaria, respectively. All diterpenes were submitted to antimicrobial assays against six different Gram-positive microorganisms to better understand the structure-activity relationship of antimicrobial diterpenes. The semi-synthetic derivatives were all obtained from the two natural derivatives by structural modifications, mainly esterification reactions. Both natural derivatives, together with the derivative ent-8(14)-pimaren-19-oic acid, displayed the most relevant antibacterial activities, with minimal inhibitory concentration (MIC) values that were less than 10 [micro]gm[L.sup.-1] for most pathogens; thus, they were considered promising antimicrobial agents. Moreover, in light of the hypothesis of Urzua and colleagues, several considerations about the structure-activity relationship of antimicrobial diterpenes could be stated. Key words: kaurane diterpenes, pimarane diterpenes, antibacterial activity, semisynthetic derivatives, structure-activity relationship. La recherche de nouveaux agents antibacteriens et d'une meilleure comprehension du comportement des substances antimicrobiennes est maintenant devenue un devoir en raison du grave probleme de sante publique que constituent les maladies infectieuses. Dans le cadre des presents travaux, nous avons etudie trente diterpenes, dont deux naturels, a savoir l'acide ent-16-kauren-19-oique et l'acide ent-pimara-8(14), 15-dien-19-oique, et 28 derives semi-synthetiques. Les diterpenes naturels ont ete isoles a partir des especes Mikania glomerata et Viguiera arenaria, respectivement. Nous avons d'abord soumis tous les diterpenes a des essais antimicrobiens contre six differents microorganismes a Gram positif, puis nous avons tente de mieux comprendre la relation structure-activite de ceux qui montraient une activite antimicrobienne. Les derives semi-synthetiques ont tous ete obtenus a partir des deux molecules naturelles par modifications structurales, principalement des reactions d'esterification. Les deux produits naturels ainsi que le derive acide ent-8(14)-pimaren-19-oique ont montre les activites antibac-teriennes les plus interessantes, soit des concentrations minimales inhibitrices (CMI) inferieures a 10 [micro]gm[L.sup.-1] contre laplupart des pathogenes, et sont donc consideres comme des agents antimicrobiens prometteurs. Par ailleurs, a la lumiere de l'hypothese d'Urzua et ses collaborateurs, nous avons pu formuler plusieurs considerations concernant la relation structure-activite des diterpenes antimicrobiens. [Traduit par la Redaction] Mots-cles : diterpenes a base de kaurane, diterpenes a base de pimarane, activite antibacterienne, derives semi-synthetiques, relation structure-activite., Introduction Natural products (NPs) are undoubtedly an impressive source of drugs, as stated by Newman and Cragg's reviews. (1) As an example, 49% of the approved small molecules by the [...]
- Published
- 2019
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