An anti-mycobacterial bisfunctionalized sphingolipid and new bromopyrrole alkaloid from the Indonesian marine sponge Agelas sp

• Published in: Journal of natural medicines Vol. 71; no. 3; pp. 531 - 536
• Main Authors: Abdjul, Delfly B., Yamazaki, Hiroyuki, Kanno, Syu-ichi, Tomizawa, Ayako, Rotinsulu, Henki, Wewengkang, Defny S., Sumilat, Deiske A., Ukai, Kazuyo, Kapojos, Magie M., Namikoshi, Michio
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.07.2017; Springer Nature B.V
• Subjects: Agelas - chemistry; Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - pharmacology; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - isolation & purification; Anti-Bacterial Agents - pharmacology; Antimicrobial agents; Biological Products - chemistry; Biological Products - pharmacology; Biomedical and Life Sciences; Biomedicine; Complementary & Alternative Medicine; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Holistic medicine; Indonesia; Marine biology; Medicinal Chemistry; Molecular Structure; Mycobacterium smegmatis - drug effects; Mycobacterium smegmatis - growth & development; Original Paper; Pharmacology/Toxicology; Pharmacy; Phytochemicals; Plant Sciences; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors; Pyrroles - chemistry; Pyrroles - isolation & purification; Pyrroles - pharmacology; Sphingolipids - chemistry; Sphingolipids - isolation & purification; Sphingolipids - pharmacology; Structure-Activity Relationship; Protein tyrosine phosphatase 1B; Marine sponge; Bromopyrrole alkaloid; Leucettamol A; sp; Mycobacterium smegmatis; Marine sponge Agelas sp
• ISSN: 1340-3443; 1861-0293
• DOI: 10.1007/s11418-017-1085-6

In the course of our studies on anti-mycobacterial substances from marine organisms, the known dimeric sphingolipid, leucettamol A ( 1 ), was isolated as an active component, together with the new bromopyrrole alkaloid, 5-bromophakelline ( 2 ), and twelve known congeners from the Indonesian marine sponge Agelas sp. The structure of 2 was elucidated based on its spectroscopic data. Compound 1 and its bis TFA salt showed inhibition zones of 12 and 7 mm against Mycobacterium smegmatis at 50 μg/disk, respectively, while the N,N’ -diacetyl derivative ( 1a ) was not active at 50 μg/disk. Therefore, free amino groups are important for anti-mycobacterial activity. This is the first study to show the anti-mycobacterial activity of a bisfunctionalized sphingolipid. Compound 13 exhibited weak PTP1B inhibitory activity (29% inhibition at 35 μM).