In vitro bactericidal activity of 3-cinnamoyl-4-hydroxy-6-methyl-2-pyrone (CHP) against drug-susceptible, drug-resistant and drug-tolerant isolates of Mycobacterium tuberculosis
| Autor: | Aehtesham Hussain, Mubashir Maqbool, Muzafar Ahmad Rather, Zahoor Ahmad, Zubair Shanib Bhat, Hafiz Ul Lah, Zuhra Jabeen, Mushtaq Ahmad Wani, Syed Khalid Yousuf |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Tuberculosis 030106 microbiology Immunology Antitubercular Agents MDR-TB Microbial Sensitivity Tests Drug resistance Microbiology Antituberculosis activity Mycobacterium tuberculosis Mice 03 medical and health sciences 0302 clinical medicine Levofloxacin medicine Animals Immunology and Allergy 030212 general & internal medicine Ethambutol Minimum bactericidal concentration biology Chemistry Isoniazid Synergism medicine.disease biology.organism_classification QR1-502 Dormant/tolerant bacilli Pharmaceutical Preparations Pyrones Cinnamoyl pyrones Rifampicin medicine.drug |
| Zdroj: | Journal of Global Antimicrobial Resistance, Vol 22, Iss, Pp 57-62 (2020) |
| ISSN: | 2213-7165 |
| Popis: | Objectives Tuberculosis (TB) poses a serious global threat to humans. New bactericidal agents that can shorten treatment duration and target drug resistance still remain a top priority in the discovery of anti-TB drugs. The objective of this study was to investigate the bactericidal potential of 3-cinnamoyl-4-hydroxy-6-methyl-2-pyrone (CHP) against drug-susceptible, drug-resistant clinical isolates and drug-tolerant Mycobacterium tuberculosis. Methods The minimum bactericidal concentration (MBC) was determined by colony-forming unit (CFU) enumeration. The kill curve analysis was done at different concentrations spanning over 16 days. Drug combination studies with antituberculosis drugs were done to investigate possible synergy. The potential against drug- resistant isolates of M. tuberculosis was done by broth dilution assay. CFU enumeration was done to determine its activity against nutrient-starved drug tolerants, and its feasibility for oral administration was tested by serum inhibitory titre. Results CHP displayed bactericidal activity with an MBC of 4 μg/mL against M. tuberculosis H37Rv. The kill curve analysis exhibited a biphasic pattern of killing. CHP showed synergy with rifampicin, isoniazid and amikacin but was indifferent towards ethambutol and levofloxacin. CHP retained its full activity against drug-susceptible, monoresistant and multidrug-resistant (MDR) clinical isolates. CHP showed very strong bactericidal activity against nondividing, drug-tolerant M. tuberculosis that on comparison was highly superior to rifampicin. Furthermore, CHP significantly improved the bactericidal activity of rifampicin and isoniazid in a combination study. The serum inhibitory titre in mice indicated its high oral bioavailability. Conclusion Our results show strong bactericidal potential of CHP against M. tuberculosis that warrant its immediate mechanistic, pharmacokinetic and pharmacodynamic studies. |
| Databáze: | OpenAIRE |
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