Planta Med 2008; 74 - PB81
DOI: 10.1055/s-0028-1084426

Antimicrobial activity of 7α-acetoxy-6β-hydroxyroyleanone 12-O-benzoyl esters

P Rijo 1, M Esteves 1, MF Simões 1, A Silva 1, A Duarte 1, B Rodriguez 2
  • 1iMed-UL, Pharmacy Faculty of Lisbon, Av. P. Gama Pinto, 1649–003 Lisbon, Portugal
  • 2IQO- CSIC, Juan Cierva 3, E-28006 Madrid, Spain

The emergence of multiple-drug-resistant bacteria strains and the arbitrary antibiotics use have highlighted the need of new strategies to treat bacterial infections that the healthcare sector has to face up [1]. Within the most important worldwide multidrug-resistant bacteria are the Gram positive cocci – methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE). Diterpenes from Plectranthus sp., mainly royleanone abietanes, exhibit antimicrobial activities [2]. Aiming to improve the known antibacterial activity of 7α-acetoxy-6β-hydroxyroyleanone (I)– MIC value of 31.25µg ml-1 against S. aureus [2], three 12-O-benzoyl derivatives (II), (III) and (IV) were prepared with suitable benzoyl chlorides. Their structures were elucidated with the usual spectroscopic means. MIC values of these compounds were evaluated against two MRSA and one VRE. 12-O-(4-Chloro) benzoyl ester (II) revealed higher activity against one MRSA and the VRE than (I). MIC values against MRSA were respectively 15.62µg ml-1 and 3.90µg ml-1 for (I) and (II). MIC's against VRE were 31.25µg ml-1 and 7.81µg ml-1 for (I) and (II), respectively. However 12-O-(4-methoxy)benzoyl (III) and 12-O-(4-nitro)benzoyl (IV) groups confer less activity (MIC values of 62.50µg ml-1 or inactivity) against MRSA or similar activity against VRE. These studies will be enlarged to clarify the role of the 12-hydroxy group and the two oxygenated position (C-6 and C-7) on activity and to attempt proposing structure-activity relationships.

(I) 7α-Acetoxy-6β-hydroxyroyleanone (II) 7α-Acetoxy-6β-hydroxy-12-O-(4-chloro)benzoylroyleanone (III) 7α-Acetoxy-6β-hydroxy-12-O-(4-methoxy)benzoylroyleanone (IV) 7α-Acetoxy-6β-hydroxy-12-O-(4-nitro)benzoylroyleanone

Acknowledgements:1 FCT–MCES (I&D n°. 8/94), POCTI (QCAIII) – FEDER, 2 Ph.D. Grant (SFRH/BD/19250/2004).

References: 1. Guella, G. et al. (2007) Anti-Infect. Agents Med. Chem. 65: 1387–90. 2. G-Marques, C. et al. (2006) Phytomedicine. 13: 267–71.