Abietane diterpenes - high value natural precursors for the development of new antimicrobial agents

ANTONIOU A.I.; FUNES CHABÁN M.; KARAGIANNI C.A.; SOLÁ C.; PALLA D.; TACHLIALBOURI M-I; CARPINELLA M. C.; ATHANASSOPOULOS C.M.

Simposio; 30 International Symposium on the Chemistry of Natural Products; 2018

Bacterial infections are dramatically increasing every day for diverse reasons, mainly due to the development of resistance to conventional antibiotics. Methicillin-resistant Staphylococcus aureus (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).Abietanes are a family of naturally occurring diterpenoids with a highly diverse repertoire of bioactivities. They have generated significant interest for the medicinal and pharmacological communities since they exhibit anticancer, antiviral, antifungal and antibacterial activity. Regarding the latter, abietane derivative are valuable in the battle against the antimicrobial resistance and imminent antibiotic shortage. In the present work, we designed and synthesized a suitable for structure-activity relationship studies (SARS) library of abietane analogues, using abietic acid as the natural precursor. Biological evaluation of these products against different S. aureus strains, methicillin-susceptible S. aureus (MSSA), CA-MRSA, HA-MRSA and LA-MRSA), revealed some promising compounds being one of them the most potent with MIC values ranging from 3.9 to 15 . Interesting results were obtained regarding the structural elements responsible for the improvement in activity. In conclusion, the synthesized compounds proved to be potential candidates for effective agents to tackle infections caused by pathogenic bacteria; especially by resistant phenotypes.