Flavonoids as Novel Efflux Pump Inhibitors and Antimicrobials Against Both Environmental and Pathogenic Intracellular Mycobacterial Species
| Autor: | Sanjib Bhakta, Franz Bucar, Julia Solnier, Liam T Martin |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
mycobacteria medicine.drug_class efflux pumps 030106 microbiology Antibiotics Pharmaceutical Science Microbial Sensitivity Tests Antimycobacterial Article Nobiletin Mycobacterium Analytical Chemistry Microbiology Agar dilution lcsh:QD241-441 03 medical and health sciences chemistry.chemical_compound Antibiotic resistance lcsh:Organic chemistry Anti-Infective Agents Bacterial Proteins Ethidium Drug Discovery medicine Physical and Theoretical Chemistry efflux pump inhibitors Flavonoids Mycobacterium Infections skullcapflavone II nobiletin Chemistry Organic Chemistry Membrane Transport Proteins Biological Transport Antimicrobial 3. Good health 030104 developmental biology Chemistry (miscellaneous) Molecular Medicine Efflux Rifampin Ethidium bromide |
| Zdroj: | Molecules Molecules, Vol 25, Iss 3, p 734 (2020) Volume 25 Issue 3 |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules25030734 |
| Popis: | Therapeutic treatment options for opportunistic non-tuberculous mycobacterial (NTM) infection and/or serious mycobacterial infections such as tuberculosis (TB) and leprosy are limited due to the spread of antimicrobial resistance mechanism. Plant-derived natural compounds as prospective efflux pump inhibitors may present a promising adjunct to conventional chemotherapy by enhancing mycobacterial susceptibility to antibiotics. This study served to evaluate the antimicrobial and resistance-modifying profile of a range of plant-derived flavonoids against the mycobacterial model strains: M. smegmatis, M. aurum, and M. bovis BCG. The minimum inhibitory concentrations (MICs) of the compounds against the mycobacterial strains were determined using both agar dilution and broth dilution assays, while their efflux inhibitory activity was investigated via an ethidium bromide-based fluorometric assay. All compounds were screened for their synergistic effects with ethidium bromide (EtBr) and rifampicin (RIF) against M. smegmatis. Skullcapflavone II (5,2&prime dihydroxy-6,7,8,6&prime tetramethoxyflavone, 1) exerted potent antimicrobial activity against M. aurum and M. bovis BCG and considerably increased the susceptibility of M. smegmatis to EtBr and RIF. Nobiletin (5,6,7,8,3&prime 4&prime hexamethoxyflavone, 2) was determined to be the most potent efflux-inhibitor in M. aurum and M. smegmatis. However, a connection between strong modulatory and putative efflux activity of the compounds could not be observed. Nevertheless, the results highlight two polymethoxyflavones, skullcapflavone II and nobiletin, with potent antimycobacterial and antibiotic resistance modulating activities as valuable adjuvants in anti-mycobacterial therapies. |
| Databáze: | OpenAIRE |
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