Antimicrobial and Efflux Pump Inhibitory Activity of Carvotacetones from Against Mycobacteria.
Huyen Thi Tran, Julia Solnier, Eva-Maria Pferschy-Wenzig, Olaf Kunert, Liam Martin, Sanjib Bhakta, Loi Huynh, Tri Minh Le, Rudolf Bauer, Franz Bucar
Author Information
Huyen Thi Tran: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitaetsplatz 4, 8010 Graz, Austria. ORCID
Julia Solnier: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitaetsplatz 4, 8010 Graz, Austria.
Eva-Maria Pferschy-Wenzig: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitaetsplatz 4, 8010 Graz, Austria. ORCID
Olaf Kunert: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Schubertstraße 1, 8010 Graz, Austria. ORCID
Liam Martin: Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
Sanjib Bhakta: Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK. ORCID
Loi Huynh: Department of Pharmacognosy, School of Medicine and Pharmacy, Da Nang University, 41 Le Duan Street, Hai Chau District, Da Nang City 550000, Vietnam.
Tri Minh Le: School of Medicine, Vietnam National University-HCMC, Quarter 6, Linh Trung Ward, Thu Duc District, HCM City 700000, Vietnam.
Rudolf Bauer: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitaetsplatz 4, 8010 Graz, Austria. ORCID
Franz Bucar: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitaetsplatz 4, 8010 Graz, Austria. ORCID
carvotacetones () isolated from were screened for their antimycobacterial and efflux pump (EP) inhibitory potential against the mycobacterial model strains mc 155, ATCC 23366, and BCG ATCC 35734. The minimum inhibitory concentrations (MICs) of the carvotacetones were detected through high-throughput spot culture growth inhibition (HT-SPOTi) and microbroth dilution assays. In order to assess the potential of the compounds and to accumulate ethidium bromide (EtBr) in and , a microtiter plate-based fluorometric assay was used to determine efflux activity. Compounds and were analyzed for their modulating effects on the MIC of EtBr and the antibiotic rifampicin (RIF) against . carvotacetones and had potent antibacterial effects on and BCG (MIC ≤ 31.25 mg/L) and could successfully enhance EtBr activity against . Compound appeared as the most efficient agent for impairing the efflux mechanism in . Both compounds and were highly effective against and BCG. In particular, compound was identified as a valuable candidate for inhibiting mycobacterial efflux mechanisms and as a promising adjuvant in the therapy of tuberculosis or other non-tubercular mycobacterial infections.
