Identification of Axinellamines A and B as Anti-Tubercular Agents.
Mar Drugs
; 22(7)2024 Jun 28.
Article
in En
| MEDLINE
| ID: mdl-39057407
ABSTRACT
Tuberculosis remains a significant global health pandemic. There is an urgent need for new anti-tubercular agents to combat the rising incidence of drug resistance and to offer effective and additive therapeutic options. High-throughput screening of a subset of the NatureBank marine fraction library (n = 2000) identified a sample derived from an Australian marine sponge belonging to the order Haplosclerida that displayed promising anti-mycobacterial activity. Bioassay-guided fractionation of the organic extract from this Haplosclerida sponge led to the purification of previously identified antimicrobial pyrrole alkaloids, axinellamines A (1) and B (2). The axinellamine compounds were found to have a 90% minimum inhibitory concentration (MIC90) of 18 µM and 15 µM, respectively. The removal of protein and complex carbon sources reduced the MIC90 of 1 and 2 to 0.6 and 0.8 µM, respectively. The axinellamines were not toxic to mammalian cells at 25 µM and significantly reduced the intracellular bacterial load by >5-fold. These data demonstrate that axinellamines A and B are effective anti-tubercular agents and promising targets for future medicinal chemistry efforts.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Porifera
/
Microbial Sensitivity Tests
/
Mycobacterium tuberculosis
/
Antitubercular Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
Mar Drugs
/
Mar. drugs
/
Marine drugs
Year:
2024
Document type:
Article