Description
Manzamine A is an alkaloid found in marine sponges. Manzamine A exhibits neuroprotective, anticancer, anti-hyperlipidemic, anti-atherosclerotic, antibiotic, and antiviral activities. In vitro, manzamine A uncouples vacuolar ATPases, inhibiting autophagy and tumor growth. Manzamine A inhibits foam cell formation in macrophages, a hallmark of atherosclerosis. Additionally, manzamine A inhibits cholesterol ester formation and acyl-CoA:cholesterol acyl-transferase (ACAT) activity in vitro and decreases total cholesterol, triglycerides, and LDL levels in vivo. This compound displays antibacterial activity against gram positive and gram negative bacteria; it may also exhibit anti-parasitic activity. In corneal cells, manzamine A inhibits viral replication and infection of herpes simplex virus a (HSV-1), inhibiting HSV-1 virion host shutoff activity. In neuroblastoma cells, manzamine A displays potential benefit in the treatment of Alzheimer’s disease by decreasing tau hyperphosphorylation and inhibiting glycogen synthase kinase 3 (GSK3).
References
Kallifatidis G, Hoepfner D, Jaeg T, et al. The marine natural product manzamine A targets vacuolar ATPases and inhibits autophagy in pancreatic cancer cells. Mar Drugs. 2013 Sep 17;11(9):3500-16. PMID: 24048269.
Eguchi K, Fujiwara Y, Hayashida A, et al. Manzamine A, a marine-derived alkaloid, inhibits accumulation of cholesterol ester in macrophages and suppresses hyperlipidemia and atherosclerosis in vivo. Bioorg Med Chem. 2013 Jul 1;21(13):3831-8. PMID: 23665143.
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Palem JR, Bedadala GR, El Sayed KA, et al. Manzamine A as a novel inhibitor of herpes simplex virus type-1 replication in cultured corneal cells. Planta Med. 2011 Jan;77(1):46-51. PMID: 20645244.
Hamann M, Alonso D, Martín-Aparicio E, et al. Glycogen synthase kinase-3 (GSK-3) inhibitory activity and structure-activity relationship (SAR) studies of the manzamine alkaloids. Potential for Alzheimer's disease. J Nat Prod. 2007 Sep;70(9):1397-405. PMID: 17708655.
Winkler JD, Londregan AT, Hamann MT. Antimalarial activity of a new family of analogues of manzamine A. Org Lett. 2006 Jun 8;8(12):2591-4. PMID: 16737321.
