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Manzamine A hydrochloride

Names

[ CAS No. ]:
104264-80-4

[ Name ]:
Manzamine A hydrochloride

Biological Activity

[Description]:

Manzamine A hydrochloride, an orally active beta-carboline alkaloid, inhibits specifically GSK-3β and CDK-5 with IC50s of 10.2 and 1.5μM, respectively. Manzamine A hydrochloride targets vacuolar ATPases and inhibits autophagy in pancreatic cancer cells. Manzamine A hydrochloride has antimalarial and anticancer activities. Manzamine A hydrochloride also shows potent activity against HSV-1[1][2][3][4].

[Related Catalog]:

Signaling Pathways >> Stem Cell/Wnt >> GSK-3
Research Areas >> Cancer
Signaling Pathways >> Anti-infection >> HIV
Research Areas >> Infection
Signaling Pathways >> Autophagy >> Autophagy
Signaling Pathways >> Cell Cycle/DNA Damage >> CDK
Research Areas >> Neurological Disease
Signaling Pathways >> PI3K/Akt/mTOR >> GSK-3
Signaling Pathways >> Membrane Transporter/Ion Channel >> Proton Pump

[Target]

GSK-3β:10.2 μM (IC50)

CDK5:1.5 μM (IC50)

HIV-1

vacuolar ATPases

Malaria


[In Vitro]

Manzamine A increases acidity in pancreatic cancer cells and non-malignant Vero cells. manzamine A is a potential inhibitor of autophagy by preventing autophagosome turnover. Manzamine A (10 µM; 2 hours; AsPC-1 cells) clearly induced an accumulation of p62 confirming an inhibition of autophagosome turnover[2]. Manzamine A represents an important lead structure for the development of novel antimalarial chemotherapies[3].

[References]

[1]. Hamann M, 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;70(9):1397-1405.

[2]. Kallifatidis G, et al. The marine natural product manzamine A targets vacuolar ATPases and inhibits autophagy in pancreatic cancer cells [published correction appears in Mar Drugs. 2014;12(4):2305-7]. Mar Drugs. 2013;11(9):3500-3516. Published 2013 Sep 17.

[3]. Winkler JD, et al. Antimalarial activity of a new family of analogues of manzamine A. Org Lett. 2006;8(12):2591-2594.

[4]. Palem JR, et al. Manzamine A as a novel inhibitor of herpes simplex virus type-1 replication in cultured corneal cells. Planta Med. 2011;77(1):46-51.

Chemical & Physical Properties

[ Molecular Formula ]:
C36H45ClN4O

[ Molecular Weight ]:
585.22

Related Compounds