 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C36H44N4O |
| Molecular Weight | 548.761 |
| Exact Mass | 584.328 |
| CAS # | 104264-80-4 |
| Related CAS # | Manzamine A;104196-68-1 |
| PubChem CID | 49797386 |
| Appearance | Light yellow to brown solid powder |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 42 |
| Complexity | 1050 |
| Defined Atom Stereocenter Count | 5 |
| SMILES | C123C([H])([H])C4(C(=C(C(C(C(C([H])([H])N4C1(C1(C(=C(c4c5[n]([H])c6c(c(c(c([H])c6c5c([H])c([H])n4)[H])[H])[H])C2([H])C([H])([H])C([H])([H])N(C(C(C(C(C(=C(C(C1([H])[H])([H])[H])[H])[H])([H])[H])([H])[H])([H])[H])([H])[H])C3([H])[H])[H])O[H])[H])([H])[H])([H])[H])([H])[H])[H])[H])[H] |
| InChi Key | DIVWQABXFSWTEF-YTGAITGWSA-N |
| InChi Code | 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 |
| Chemical Name | (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 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | GSK-3β 10.2 μM (IC50) Plasmodium CDK5 1.5 μM (IC50) vacuolar ATPases Malaria HSV-1 |
| ln Vitro | Manzamine A (5-50 µM, 18 h) hydrochloride reduces tau phosphorylation as determined by ELISA[1]. Manzamine A (10 µM) hydrochloride inhibits 30% of the development of yeast S. cerevisiae[2]. In yeast, manzamine A hydrochloride exhibits a few expanded vacuoles[2]. Pancreatic cancer cells and non-malignant Vero cells exhibit increased acidity in response to manzamine A (2.5-10 µM, 24 h) hydrochloride[2]. In SIRC cells, HSV-1 infection is inhibited by manzamine A (1 µM, 24 h) hydrochloride[4]. The antimalarial activity of manzamine A hydrochloride is demonstrated by IC50 values of 8.0 nM (D6 clone) and 11 nM (W2 clone)[5]. |
| ln Vivo | Infected mice treated with manzamine A (50 and 100 mol/kg, po or ip) hydrochloride do not develop the rodent malaria parasite Plasmodium berghei [6]. Swine survival is extended to 20 days with manzamine A (8 mg/kg, ip, daily for 8 consecutive days) hydrochloride[7]. |
| Cell Assay |
Cell Viability Assay[4] Cell Types: SIRC cell Tested Concentrations: 0.1, 0.5, 1, 2, 3, 5, and 10 µM Incubation Duration: 72 h Experimental Results: Inhibited SIRC cell viability with an IC50 of 5.6 µM. |
| Animal Protocol |
Animal/Disease Models: Plasmodium berghei in infected mice[6] Doses: 50 or 100 mol/kg Route of Administration: intraperitoneal (ip)injection or oral administration (po) Experimental Results: Inhibited the growth of the rodent malaria parasite Plasmodium berghei. Prolonged the survival of highly parasitaemic mice. |
| References |
[1]. 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]. 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]. Antimalarial activity of a new family of analogues of manzamine A. Org Lett. 2006;8(12):2591-2594. [4]. 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]. 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]. Marine natural products and their potential applications as anti-infective agents. Lancet Infect Dis. 2003 Jun;3(6):338-48. [7]. New manzamine alkaloids with potent activity against infectious diseases. J Am Chem Soc. 2001 Mar 7;123(9):1804-8. |
Solubility Data
| Solubility (In Vitro) | DMSO : 5.88 mg/mL (10.05 mM) |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8223 mL | 9.1115 mL | 18.2229 mL | |
| 5 mM | 0.3645 mL | 1.8223 mL | 3.6446 mL | |
| 10 mM | 0.1822 mL | 0.9111 mL | 1.8223 mL |