Antibacterial compounds isolated from Lepechinia meyenii and synthesis of analogues with improved activity

FUNES CHABÁN M.; ANTONIOU A.I.; JORAY M.B.; KARAGIANNI C.A.; SOLÁ C.; BOCCO J.L.; CRESPO M.I.; PALACIOS S. M.; ATHANASSOPOULOS C.M.; CARPINELLA M.C

Simposio; COST Action CM1407 Challenging organic synthesis inspired by nature-form natural products chemistry to drug discovery; 2017

Bacterial infections are dramatically increasing every day for diverse reasons, mainly due to the development of resistance to conventional antibiotics. Staphylococcus aureus resistant to methicillin and gentamicin (MRSA) is one of the major pathogen being responsible for 60-89% of nosocomial infections. The urgent need to develop new antibiotics to deal with ever more resistant bacteria is therefore of great interest to researchers and pharmaceutical industries.Plants have played a dominant role in the development of sophisticated traditional medicine systems. The chemodiversity in nature offers a valuable source of new drugs, new drug leads, and new chemical entities (NCEs). Although many plant families have been investigated, the plant world is far from being totally explored and this also applies to the native flora from Argentina. In our ongoing effort to identify antibacterial agents of plant origin, sixty nine native plants from central Argentina were screened against Enterococcus faecalis, methicillin- susceptible S. aureus (MSSA), MRSA, CA-MRSA, HA-MRSA and LA-MRSA. Extract from Lepechinia meyenii (Walp.) Epling showed itself the most effective with MIC values ranging from 32 to125 Ug/ml, showing an outstanding selectivity against all MRSA strains. Bioguided fractionation led to the isolation of carnosol and rosmanol as its active principles with MIC values ranging from 9 to 62 and 15 to 125 Ug/ml, respectively.Analogues of the isolated diterpenes with improved activity were obtained synthetically from abietic acid. Among them, two promising compounds showed MIC values ranging from 7 to 125 Ug/ml against the bacteria tested. A structure-activity relationship will be described in detail.The results obtained positioned these compounds as potential candidates for effective agents to tackle infections caused by pathogenic bacteria; especially by resistant phenotypes.