Synthesis and structure?activity relationships of novel abietane diterpenoids with activity against Staphylococcus aureus

FUNES CHABÁN, MACARENA; TOUMPA DIMITRA ; SOLA, CLAUDIA; KARAGIANNI CATHERINE ; BOCCO, JOSÉ LUIS; CARPINELLA, MARÍA CECILIA; ANTONIOU, ANTONIA; JORAY, MARIANA BELÉN; ATHANASSOPOULOS, CONSTANTINOS

Future Medicinal Chemistry

Future Science

Año: 2019

1756-8919

Aim: To find alternative compounds against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA), novel derivatives from dehydroabietic acid were synthesized.Methods & results: Compound 12 was the most effective against 15 MRSA and 11 MSSA with minimum inhibitory concentration values ranging from 3.9 to 15.6 μg/ml. Although less active than 12, compound 11, followed by 25 and 13, also exhibited anti-staphylococcal activity. Additional studies showed that compound12 is devoid of toxic effect on non-target cells. A structure?activity relationship study revealed that an oxime at C-13 together with a hydroxyl at C-12 could play a key role in the activity. Conclusion: These structures, in particular compound 12, could arise as templates for the development of agents against MRSA and MSSA.