Synergistic Effects Between Thioxanthones and Oxacillin Against Methicillin-Resistant Staphylococcus aureus

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Lucinda J Bessa (Author) Other; Andreia Palmeira (Author) Other; Ana S Gomes (Author) Other; Vitor Vasconcelos (Author) FCUP; Emilia Sousa (Author) Other; Madalena Pinto (Author) Other; Paulo Martins da Costa (Author) Other

Journal

Title: Microbial Drug Resistance

Vol. 21

Pages: 404-415

ISSN: 1076-6294

Publisher: Mary Ann Liebert

Indexing

ISI Web of Knowledge - 24 Citations

Scopus - 28 Citations

Scientific classification

FOS: Medical and Health sciences > Health sciences

Other information

Authenticus ID: P-00G-EFQ

DOI: 10.1089/mdr.2014.0162

Abstract (EN): The extensive use of antimicrobials is leaving medicine with few effective therapeutic options to treat many infections due to the fact that many organisms developed resistance to commonly used drugs. It is therefore pertinent to search not only for new antimicrobials but also for compounds able to restore or potentiate the activity of existing antibiotics. We have screened a library consisting of 40 (thio)xanthone derivatives for antibacterial activity and possible synergistic effects when used in combination with antibiotics. Nine out of the 40 compounds exhibited antibacterial activity against Gram-positive bacteria. Two xanthone derivatives, 1-formyl-4-hydroxy-3-methoxy (7), 2-formyl-3-hydroxy-4-methoxyxanthone (8) and the thioxanthone derivative 1-((2-(diethylamino)ethyl)amino)-4-propoxythioxanthone (10) and its hydrochloride form 13, showed activity against a methicillin-resistant Staphylococcus aureus (MRSA) isolate with minimum inhibitory concentration (MIC) values lower than 256g/ml. Thioxanthone 10 demonstrated antibacterial activity and also synergy when combined with ampicillin and oxacillin against MRSA. Additionally, thioxanthone 1-(piperidin-1-yl)-4-propoxythioxanthone (9), despite not having antibacterial activity presented remarkable synergy with oxacillin against MRSA; the MIC of tioxanthone 9 and oxacillin when both were in combination were 128 and 8g/ml, respectively. Thioxanthones 9 and 10 were also found to be synergistic when both were combined. Subsequently, docking simulations between thioxanthones 9 and 10 and the allosteric domain of penicillin-binding protein 2A (PBP2A) were undertaken in AutoDock Vina. Both compounds had the ability to bind with an allosteric domain of PBP2A, which may explain their synergy with oxacillin. These two thioxanthone derivatives with different profiles may be promising tools for restoring the activity of oxacillin against MRSA.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12