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 .
Karumanchi V. Rao,Marwa S. Donia,Jiangnan Peng,Esther Garcia-Palomero,Diana Alonso,Ana Martinez,Miguel Medina,Scott G. Franzblau,Babu L. Tekwani,Shabana I. Khan,Subagus Wahyuono,Kristine L. Willett, and Mark T. Hamann*
School of Pharmacy and the National Center for Natural Products Research, The University of Mississippi, University, Mississippi 38677, Neuropharma, S.A., Avenida De la Industria, 52, 28760 Tres Cantos, Madrid, Spain, Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60607, and Department of Pharmaceutical Biology, Faculty of Pharmacy, Gadjah Mada University, Yogyakarta 55281, Indonesia
Abstract:
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.