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.
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.
Rao
Karumanchi V
KV
School of Pharmacy and the National Center for Natural Products Research, The University of Mississippi, University, Mississippi 38677, USA.
Donia
Marwa S
MS
Peng
Jiangnan
J
Garcia-Palomero
Esther
E
Alonso
Diana
D
Martinez
Ana
A
Medina
Miguel
M
Franzblau
Scott G
SG
Tekwani
Babu L
BL
Khan
Shabana I
SI
Wahyuono
Subagus
S
Willett
Kristine L
KL
Hamann
Mark T
MT
D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D007214:Indonesia; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009990:Oryzias / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects; D011161:Porifera / Q000737:chemistry*; D013329:Structure-Activity Relationship
D026121:Indole Alkaloids; C513454:ircinal A; C513455:manzamine B; C513456:manzamine E; D038362:Glycogen Synthase Kinase 3