Manzamine B and E and Ircinal A Related Alkaloids from an Indonesian Acanthostrongylophora Sponge and Their Activity against Infectious, Tropical Parasitic, and Alzheimer's Diseases

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2006-07, Vol.69 (7), p.1034-1040
• Main Authors: Rao, Karumanchi V, Donia, Marwa S, Peng, Jiangnan, Garcia-Palomero, Esther, Alonso, Diana, Martinez, Ana, Medina, Miguel, Franzblau, Scott G, Tekwani, Babu L, Khan, Shabana I, Wahyuono, Subagus, Willett, Kristine L, Hamann, Mark T
• Format: Article
• Language: English
• Subjects: Acanthostrongylophora; alkaloids; Alzheimer Disease - pathology; Animals; bioactive properties; Biological and medical sciences; chemical structure; Female; General pharmacology; Glycogen Synthase Kinase 3 - antagonists & inhibitors; HIV-1 - drug effects; Human immunodeficiency virus 1; Humans; hydroxymanzamine; Indole Alkaloids - chemistry; Indole Alkaloids - isolation & purification; Indole Alkaloids - pharmacology; Indonesia; Inhibitory Concentration 50; Leishmania; Leishmania donovani - drug effects; manzamine; Marine; Medical sciences; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium; Mycobacterium tuberculosis - drug effects; Oryzias - metabolism; Oryzias latipes; oxaircinal; oxamanzamine; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plasmodium falciparum - drug effects; Porifera; Porifera - chemistry; spectral analysis; Structure-Activity Relationship
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np0601399

Four new manzamine-type alkaloids, 12,28-oxamanzamine E (2), 12,34-oxa-6-hydroxymanzamine E (3), 8-hydroxymanzamine B (5), and 12,28-oxaircinal A (11), were isolated from three collections of an Indonesian sponge of the genus Acanthostrongylophora together with 13 known manzamine alkaloids, ircinal A, ircinol A, xestomanzamine A, manzamines A, E, F, J, and Y, manadomanzamines A and B, neo-kauluamine, 8-hydroxymanzamine A, and manzamine A N-oxide. The structures of the new compounds were elucidated by means of 1D and 2D NMR spectroscopic methods. Three of these compounds (2, 3, and 11) possess a unique manzamine-type aminal ring system generated through an ether linkage between carbons 12−28 or between carbons 12−34. In the case of manzamine B and related metabolites, carbons 11 and 12 of the typical manzamine structure have an epoxide group and add to our growing understanding of manzamine structure−activity relationships (SAR) and metabolism. The bioactivity and SAR for a number of previously reported manzamine-related metabolites against malaria, leishmania, tuberculosis, and HIV-1 are also presented. Manzamine Y (9) showed significant inhibitory activity of GSK3, an enzyme implicated in Alzheimer's disease pathology. The toxicity of manzamine A and neo-kauluamine was evaluated against both medaka fry and eggs.