Abietane diterpenoids isolated from Lepechinia meyenii (Walp.) Epling: study of mechanism of action

FUNES CHABÁN M.; HARST MARTINA; JORAY M.B.; PETERLIN, LUCIJA; KIKELJ D.; CARPINELLA M. C.

Congreso; Reunión Anual de Sociedades de Biociencia. SAIC SAFE SAB SAP AACYTAL NANOMED-ar HCS; 2019

Nowadays, the management of bacterial infections is a great challenge of therapeutics mainly due to the development of resistant strains against several antibiotics. Staphylococcus aureus is one of the most prevalent pathogens worldwide. In this context, methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) represent a serious public health threat. This scenario results in the urgent need to find novel and safe compounds to develop antibiotics to control infections caused by bacteria.Peptidoglycan is the major component of the bacterial cell wall and its function is to provide shape and rigidity, protect against osmotic changes and plays an important role in the process of cell division, so its inhibition is considered an important target in antibacterial therapy, mainly of the enzymes involved in the cytoplasmic stage of the biosynthesis such as MurA-F.Since prehistory mankind has turned to nature to treat several diseases and plants have been used by various civilizations and cultures in folk medicine. The bioguided fractionation of the medicinal plant Lepechinia meyenii led to the isolation of carnosol (1), rosmanol (2) and carnosic acid (3) as active principles effective mainly against MRSA and MSSA strains. Studies of mechanisms of action in inhibition of MurA and MurF enzymes from Escherichia coli and S. aureus were carried out using the colorimetric malachite green method in which orthophosphate generated during reaction is measured. Compounds 1-3 were able to inhibit MurA from S. aureus and E. coli showing IC50 values of 1.1-5.7-12 and 37-74-27 µM, respectively. However, none of the diterpenes isolated was able to inhibit MurF from S. aureus and E. coli.The results obtained showed that compounds 1-3 exert their antibacterial activity by the inhibition of MurA enzyme.