INSTITUTO DE INVESTIGACIONES EN RECURSOS NATURALES Y SUSTENTABILIDAD JOSE SANCHEZ LABRADOR S.J.
Unidad Ejecutora - UE
congresos y reuniones científicas
Natural aromatic abietanes obtained from Lepechinia meyenii and semi-synthetic derivatives with antibacterial activity against methicillinresistant Staphylococcus aureus
KARAGIANNI C.A.; SOLÁ C.; ATHANASSOPOULOS C.M.; JORAY M.B.; CARPINELLA M. C.; FUNES CHABÁN M.; TOUMPA D.
Encuentro; Cost Action 1407; 2018
Nowadays bacterial infections are becoming a severe health problem, mainly due to the development of strains with resistance against conventional antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) is considered a serious threat to international health care.Therefore, in both academia and pharmaceutical industries is clear that there is an urgent need for the development of new antibiotics, able to deal with ever more resistant bacteria.Plants have always played a dominant role in drug discovery, offering a valuable source of new chemical entities (NCEs), new drugs and new drug leads.In our ongoing effort to identify antibacterial agents of plant origin, sixty-eight native plants from central Argentina were screened against methicillin- susceptible S. aureus (MSSA)and CA-MRSA, HA-MRSA and LA-MRSA strains. Extract from Lepechinia meyenii showed itself to be the most effective with MIC values ranging from 62.5 to 500 μg/mL. showing anoutstanding selectivity against all the MRSA strains assayed. Bioguided fractionation led to the isolation of carnosol (1), rosmanol (2) and carnosic acid (3) as active principles, with minimum inhibitory concentration (MIC) values ranging from 15.6-31.2, 15.6-62.5 and 7.8-15.6 μg/mL, respectively against 15 MRSAs and 15.6-31.2, 31.2-62.5 and 7.8-15.6 μg/mL,respectively against 11 MSSA strains.In order to identify the structural elements, being responsible for the antibacterial activity of 1-3, four key derivatives of carnosic acid (3) were synthesized. The activity results obtained showed that the OH-12 group is necessary for an outstanding activity and that the methylation of C-20 proved to significantly increase the effectiveness, as observed with methyl carnosate (5). The latter displayed greater effect than 3 with MIC values of 3.8 μg/mL against all the MRSA and 1.9-3.8 μg/mL against the MSSA. The structure-activity analysis of compounds 1-7 shed light for the design of novel antibacterial agents, especially those able to circumvent infections involving resistant S. aureus