Manzamine A hydrochloride

• CAT Number: I045552
• CAS Number: 104264-80-4
• Molecular Formula: C36H45ClN4O
• Molecular Weight: 585.22
• Purity: ≥95%
• Synonyms: (1R,2R,4R,5Z,12R,13S,16Z)-25-(9H-pyrido[3,4-b]indol-1-yl)-11,22-diazapentacyclo[11.11.2.12,22.02,12.04,11]heptacosa-5,16,25-trien-13-ol;hydrochloride
• InChI: InChI=1S/C36H44N4O.ClH/c41-36-18-10-4-1-2-5-11-20-39-22-17-30(35(25-39)23-26-13-7-3-6-12-21-40(26)34(35)36)29(24-36)32-33-28(16-19-37-32)27-14-8-9-15-31(27)38-33;/h1,4,7-9,13-16,19,24,26,30,34,38,41H,2-3,5-6,10-12,17-18,20-23,25H2;1H/b4-1-,13-7-;/t26-,30-,34+,35-,36-;/m0./s1
• InChIKey: DIVWQABXFSWTEF-YTGAITGWSA-N
• SMILES: C1CCN2CCC3C(=CC(CCC=CC1)(C4C3(C2)CC5N4CCCCC=C5)O)C6=NC=CC7=C6NC8=CC=CC=C78.Cl

Manzamine A hydrochloride, 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 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].
Manzamine A (5-50 µM, 18 h) hydrochloride decreases tau phosphorylation, measured with ELISA[1].
Manzamine A (10 µM) hydrochloride inhibits yeast S. cerevisiae growth by 30%[2].
Manzamine A hydrochloride displays a few enlarged vacuoles in yeast[2].
Manzamine A (2.5-10 µM, 24 h) hydrochloride increases acidity in pancreatic cancer cells and non-malignant Vero cells[2].
Manzamine A (1 µM, 24 h) hydrochloride inhibits HSV-1 infection in SIRC cells[4].
Manzamine A hydrochloride shows antimalarial activity with an IC50 of 8.0 nM (D6 clone) and 11 nM (W2 clone)[5].
Manzamine A (50 and 100 mol/kg, p.o. or i.p.) hydrochloride 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) hydrochloride prolongs the survival of SW mice to 20 days[7].

Reference

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