beta-Acetyldigoxin ;

(3b,5b,12b)-3-[(O-4-O-Acetyl-2,6-dideoxy-b-D-ribo-hexopyranosyl-(14)-O-2,6-dideoxy-b-D-ribo-hexopyranosyl-(14)-2,6-dideoxy-b-D-ribo-hexopyranosyl)oxy]-12,14-dihydroxycard-20(22)-enolide; Digoxigenin Tridigitoxoside-b-acetate; 16'-Acetyldigoxin; Novodigal

Beta-acetyldigoxin, also known as acetyldigoxin, is a cardiac glycoside drug obtained from the leaves of Digitalis lanata. It is widely used in the treatment of congestive heart failure and atrial fibrillation due to its ability to increase the force and rate of cardiac contractions. The drug acts by inhibiting the Na+/K+-ATPase enzyme, which leads to an increase in intracellular calcium concentration and subsequent contraction of the cardiac muscle.

Synthesis and Characterization

Beta-acetyldigoxin can be synthesized by the acetylation of digoxin, another cardiac glycoside drug, using acetic anhydride and anhydrous sodium acetate. The reaction yields beta-acetyldigoxin and acetic acid as by-products. The purity of beta-acetyldigoxin can be determined using high-performance liquid chromatography (HPLC) or gas chromatography (GC) techniques.

Analytical Methods

Beta-acetyldigoxin can be quantified in biological matrices, such as blood, serum, and urine, using various analytical methods, including immunoassay, HPLC, GC, and mass spectrometry. Immunoassay techniques, such as enzyme-linked immunosorbent assay (ELISA), are commonly used for the rapid detection of beta-acetyldigoxin in clinical settings.

Biological Properties

Beta-acetyldigoxin has a longer half-life and higher potency than digoxin, which makes it more effective in the treatment of congestive heart failure and atrial fibrillation. It has a narrow therapeutic window and requires careful monitoring to avoid toxicity. Beta-acetyldigoxin is metabolized by the liver and excreted via the kidneys.

Toxicity and Safety in Scientific Experiments

Beta-acetyldigoxin can cause serious adverse effects, including arrhythmias, nausea, vomiting, and visual disturbances. The toxicity of beta-acetyldigoxin can be assessed in animal models using various techniques, such as electrocardiography, tissue histology, and blood chemistry analysis. The safety of beta-acetyldigoxin in clinical trials is monitored using various parameters, such as the incidence of adverse events, vital signs, and laboratory test results.

Applications in Scientific Experiments

Beta-acetyldigoxin is used in scientific experiments to study the mechanism of action of cardiac glycosides and their effect on the heart and other organs. It is also used to test the efficacy of new drugs for the treatment of cardiac diseases and to evaluate drug interactions.

Current State of Research

Beta-acetyldigoxin has been extensively studied for its therapeutic potential in cardiology. However, the current state of research is focused on the discovery of new cardiac glycosides with enhanced efficacy and reduced toxicity. Recent studies have also investigated the potential of beta-acetyldigoxin in the treatment of cancer and other diseases.

Potential Implications in Various Fields of Research and Industry

Beta-acetyldigoxin has potential applications in various fields of research and industry, such as the development of new drugs for cardiac diseases, the production of high-value chemicals using biotechnology, and the development of biosensors for rapid detection of beta-acetyldigoxin in biological samples.

Limitations and Future Directions

The limitations of beta-acetyldigoxin include its narrow therapeutic window, potential for toxicity, and limited availability. Future directions in the research of beta-acetyldigoxin include the development of new drugs with improved safety and efficacy, the exploration of new applications in cancer and other diseases, and the optimization of production processes using biotechnology.

Some Future Directions for beta-Acetyldigoxin

1. Investigating the efficacy of beta-acetyldigoxin in combination with other drugs for the treatment of cardiac diseases.

2. Developing novel formulations of beta-acetyldigoxin that can overcome its limitations and enhance its therapeutic potential.

3. Exploring the potential of beta-acetyldigoxin in the treatment of other diseases, such as cancer and neurological disorders.

4. Developing biosensors for the rapid detection of beta-acetyldigoxin in biological samples.

5. Optimizing the production of beta-acetyldigoxin using biotechnology and synthetic biology.

6. Investigating the mechanisms of toxicity of beta-acetyldigoxin and developing strategies to mitigate its adverse effects.

7. Developing novel analogues of beta-acetyldigoxin with improved pharmacokinetic and pharmacodynamic properties.

8. Studying the role of beta-acetyldigoxin in the regulation of ion channels and intracellular signaling pathways.

9. Investigating the potential of beta-acetyldigoxin in the prevention and treatment of cardiovascular diseases in high-risk populations.

10. Developing personalized dosing regimens for beta-acetyldigoxin based on individual patient characteristics.

Title: Digoxin

CAS Registry Number: 20830-75-5

CAS Name: (3b,5b,12b)-3-[(O-2,6-Dideoxy-b-D-ribo-hexopyranosyl-(1®4)-O-2,6-dideoxy-b-D-ribo-hexopyranosyl-(1®4)-2,6-dideoxy-b-D-ribo-hexopyranosyl)oxy]-12,14-dihydroxycard-20(22)-enolide

Trademarks: Digacin (Beiersdorf-Lilly); Dilanacin (AWD); Eudigox (Simes); Lanicor (Roche); Lanoxin (GSK); Lanoxicaps (GSK); Lenoxin (GSK); Neo-Dioxanin (Boehringer, Ing.); Rougoxin (Rougier)

Molecular Formula: C41H64O14

Molecular Weight: 780.94

Percent Composition: C 63.06%, H 8.26%, O 28.68%

Literature References: Secondary glycoside from Digitalis lanata Ehrh., or D. orientalis Lam., Scrophulariaceae: S. Smith, J. Chem. Soc. 1930, 508; Stoll, The Cardiac Glycosides (London, 1937); M. M. Dhar et al., IN 62497 (1958 to Council Sci. Indust. Res.), C.A. 53, 653b (1959). See also ref under Digoxigenin. Acid hydrolysis of digoxin yields 1 mol digoxigenin + 3 mols digitoxose. The sugar residue is attached to the hydroxyl group at C-3 of the aglycon. Clinical pharmacokinetics: J. K. Aronson, Clin. Pharmacokinet. 5, 137 (1980). Comprehensive description: P. R. B. Foss, S. A. Benezra, Anal. Profiles Drug Subs. 9, 207-243 (1980).

Properties: Radially arranged, four- and five-sided triclinic plates from dil alcohol or dil pyridine, decomp 230-265°. [a]25Hg +13.4 to 13.8° (c = 10 in pyridine). uv max (ethanol): 220 nm (e 12800). Sol in dil alcohol, pyridine, or mixt of chloroform and alcohol. Almost insol in ether, acetone, ethyl acetate, chloroform, water. More sol in hot 80% alcohol than gitoxin.

Optical Rotation: [a]25Hg +13.4 to 13.8° (c = 10 in pyridine)

Absorption maximum: uv max (ethanol): 220 nm (e 12800)

Derivative Type: b-Methyldigoxin

CAS Registry Number: 30685-43-9

Additional Names: Medigoxin; metildigoxin; 4¢¢¢-O-methyldigoxin; 3b,12b,14b-trihydroxy-5b-card-20(22)-enolide-3-(4¢¢¢-O-methyltridigitoxoside)

Trademarks: Cardiolan (Tosi); Lanirapid (Roche); Lanitop (Roche)

Molecular Formula: C42H66O14

Molecular Weight: 794.97

Percent Composition: C 63.46%, H 8.37%, O 28.18%

Literature References: Obtained by the O-methylation of digoxin: F. Kaiser et al., ZA 6806079; eidem, US 3538078 (1969, 1970 both to Boehringer, Mann.). Pharmacology and toxicity studies: W. Schaumann, R. Wegerle, Arzneim.-Forsch. 21, 225 (1971); H. Czerwek et al., ibid. 231.

Properties: Crystals, mp 227-231°. LD50 in rats, mice (mg/kg): 4.8, 4.9 i.v.; 6.2, 4.8 i.p.; 8.3, 7.8 orally (Czerwek).

Melting point: mp 227-231°

Toxicity data: LD50 in rats, mice (mg/kg): 4.8, 4.9 i.v.; 6.2, 4.8 i.p.; 8.3, 7.8 orally (Czerwek)

Derivative Type: a-Acetyldigoxin

CAS Registry Number: 5511-98-8

Trademarks: Lanatilin (Wabosan); Sandolanid (Sandoz)

Molecular Formula: C43H66O15

Molecular Weight: 822.98

Percent Composition: C 62.75%, H 8.08%, O 29.16%

Properties: Obtained by enzymatic hydrolysis of digilanide. Prisms from methanol + chloroform, dec 225°. [a]D20 +18.9° (pyridine). Very sparingly sol in ethyl acetate.

Optical Rotation: [a]D20 +18.9° (pyridine)

Derivative Type: b-Acetyldigoxin

CAS Registry Number: 5355-48-6

Trademarks: Kardiamed (Medice); Longdigox (Trommsdorff); Novodigal (Beiersdorf-Lilly); Stillacor (Wolff)

Properties: Needles from alcohol + chloroform, dec 240°. [a]D20 +30.4° (c = 1.2 in alc). More sol in ethyl acetate than the a-form.

Optical Rotation: [a]D20 +30.4° (c = 1.2 in alc)

Therap-Cat: Cardiotonic.

Therap-Cat-Vet: Cardiotonic.

Keywords: Cardiotonic.