期刊
FRONTIERS IN MICROBIOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fmicb.2020.622629
关键词
Mycobacterium tuberculosis; drug discovery; natural product; synthetic polyacetylenes; antimicrobial drug resistance
类别
资金
- CNPq
- CAPES
- Wellcome Trust Institutional Strategic Support Fund [204833/Z/16/A, 204538/Z/16/Z]
- University of Brighton Santander Travel Award
- Wellcome Trust [204833/Z/16/A, 204538/Z/16/Z] Funding Source: Wellcome Trust
The study tested a library of 52 natural and synthetic compounds and identified seven compounds with antimycobacterial activity, suggesting new avenues for drug discovery.
Drug-resistant tuberculosis threatens to undermine global control programs by limiting treatment options. New antimicrobial drugs are required, derived from new chemical classes. Natural products offer extensive chemical diversity and inspiration for synthetic chemistry. Here, we isolate, synthesize and test a library of 52 natural and synthetic compounds for activity against Mycobacterium tuberculosis. We identify seven compounds as antimycobacterial, including the natural products isobavachalcone and isoneorautenol, and a synthetic chromene. The plant-derived secondary metabolite damnacanthal was the most active compound with the lowest minimum inhibitory concentration of 13.07 mu g/mL and a favorable selectivity index value. Three synthetic polyacetylene compounds demonstrated antimycobacterial activity, with the lowest MIC of 17.88 mu g/mL. These results suggest new avenues for drug discovery, expanding antimicrobial compound chemistries to novel anthraquinone and polyacetylene scaffolds in the search for new drugs to treat drug-resistant bacterial diseases.
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