Keramamine A

Names

[ Name ]:
Keramamine A

[Synonym ]:
(4S)-1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic Acid 2-[4-(Diphenylmethyl)-1-piperazinyl]ethyl Methyl Ester
(+)-manidipine
(S)-Manidipine
MANZAMINE A

Biological Activity

[Description]:

Manzamine A, an orally active beta-carboline alkaloid, inhibits specifically GSK-3β and CDK-5 with IC50s of 10.2 μM and 1.5 μM, respectively. Manzamine A targets vacuolar ATPases and inhibits Autophagy in pancreatic cancer cells. Manzamine A has antimalarial and anticancer activities. Manzamine A 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 >> HSV

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]

Plasmodium

GSK-3β:10.2 μM (IC50)

CDK5:1.5 μM (IC50)

vacuolar ATPases

Malaria

HSV-1

[In Vitro]

Manzamine A (5-50 µM, 18 h) decreases tau phosphorylation, measured with ELISA[1]. Manzamine A (10 µM) inhibits yeast S. cerevisiae growth by 30%[2]. Manzamine A displays a few enlarged vacuoles in yeast[2]. Manzamine A (2.5-10 µM, 24 h) increases acidity in pancreatic cancer cells and non-malignant Vero cells[2]. Manzamine A (1 µM, 24 h) inhibits HSV-1 infection in SIRC cells[4]. Manzamine A shows antimalarial activity with an IC50 of 8.0 nM (D6 clone) and 11 nM (W2 clone)[5]. Cell Viability Assay[4] Cell Line: SIRC cell Concentration: 0.1, 0.5, 1, 2, 3, 5, and 10 µM Incubation Time: 72 h Result: Inhibited SIRC cell viability with an IC50 of 5.6 µM.

[In Vivo]

Manzamine A (50 and 100 mol/kg, p.o. or i.p.) inhibits the growth of the rodent malaria parasite Plasmodium berghei in infected mice[6]. Manzamine A (8 mg/kg, i.p., daily for 8 consecutive days) prolongs the survival of SW mice to 20 days[7]. Animal Model: Plasmodium berghei in infected mice[6] Dosage: 50 or 100 mol/kg Administration: Intraperitoneal injection (i.p.) or oral administration (p.o.) Result: Inhibited the growth of the rodent malaria parasite Plasmodium berghei. Prolonged the survival of highly parasitaemic mice.

[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.

[5]. Wahba AE, et al. Structure-activity relationship studies of manzamine A: amidation of positions 6 and 8 of the beta-carboline moiety. Bioorg Med Chem. 2009 Nov 15;17(22):7775-82.

[6]. Donia M, et al. Marine natural products and their potential applications as anti-infective agents. Lancet Infect Dis. 2003 Jun;3(6):338-48.

[7]. El Sayed KA, et al. New manzamine alkaloids with potent activity against infectious diseases. J Am Chem Soc. 2001 Mar 7;123(9):1804-8.

Chemical & Physical Properties

[ Density]:
1.26g/cm3

[ Boiling Point ]:
756.6ºC at 760mmHg

[ Molecular Formula ]:
C₃₆H₄₄N₄O

[ Molecular Weight ]:
548.76100

[ Flash Point ]:
411.4ºC

[ Exact Mass ]:
548.35200

[ PSA ]:
55.39000

[ LogP ]:
6.73160

[ Vapour Pressure ]:
4.65E-24mmHg at 25°C

[ Index of Refraction ]:
1.701

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds

The content on this webpage is sourced from various professional data sources. If you have any questions or concerns regarding the content, please feel free to contact service1@chemsrc.com.