104196-68-1

104196-68-1 structure

Name: Keramamine A
Chemical Name: manzamine A
CAS Number: 104196-68-1
Molecular Formula: C₃₆H₄₄N₄O
Molecular Weight: 548.76100
Catalog: Signaling Pathways Anti-infection HSV
Create Date: 2016-01-20 15:13:10
Modify Date: 2024-01-03 21:45:19
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].

Name	manzamine A
Synonyms	(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

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.

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

139975-55-6

104196-68-1

Literature: Choo, Yeun-Mun; Hamann, Mark T. Heterocycles, 2007 , vol. 71, # 2 p. 245 - 252

61-54-1

104196-68-1

Literature: Choo, Yeun-Mun; Hamann, Mark T. Heterocycles, 2007 , vol. 71, # 2 p. 245 - 252

159898-15-4

104196-68-1

Literature: Jakubec, Pavol; Hawkins, Alison; Felzmann, Wolfgang; Dixon, Darren J. Journal of the American Chemical Society, 2012 , vol. 134, # 42 p. 17482 - 17485

Precursor 2
61-54-1 159898-15-4
DownStream 0

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