Diogoxin

July 18, 2022
I may be good for your heart, but take me cautiously.
What molecule am I?
Image of Diogoxin 3D Image of Diogoxin

Digoxin is a secondary glycoside produced by plants in the Digitalis (foxglove) genus that were used for medicinal purposes as long ago as the 18th century. In 1930, Sydney Smith at Burroughs Wellcome (London) isolated it from one species, D. lanata. 

The US Food and Drug Administration approved the use of digoxin as a heart-disease medication in the late 1990s. It has been prescribed ever since under trade names such as Lanoxin for atrial fibrillation and heart failure. Digoxin, however, has a narrow therapeutic index; and drug interactions and adverse side effects are common. It has shown efficacy against some cancers, but other studies indicated that patients on digoxin have an increased risk of developing cancer.

Overdose is often fatal, as shown in the hazard information table. In 2003, a hospital nurse pleaded guilty to killing as many as 40 patients with digoxin and other heart medications.

Digoxin should not be confused with digitoxin1, which has one fewer hydroxyl group and is also a heart medication. For a new wrinkle on digoxin, see Molecule of the Future below.

1. CAS Reg. No. 71-63-6.

Digoxin ether hazard information

Hazard class* GHS code and hazard statement
Acute toxicity, oral , category 2 H300—Fatal if swallowed  Chemical Safety Warning
Acute toxicity, inhalation , category 3 H331—Toxic if inhaled Chemical Safety Warning
Carcinogenicity, category 2 H351—Suspected of causing cancer Chemical Safety Warning
Specific target organ toxicity, repeated exposure, category 2 H373—May cause damage to organs through prolonged or repeated exposure Chemical Safety Warning

*Globally Harmonized System (GHS) of Classification and Labeling of Chemicals. Explanation of pictograms

Molecule of the Future

According to Xiang-Guo Hu, Chu-Yi Yu, and colleagues at Jiangxi Normal University (Nanchang, China) and the Chinese Academy of Sciences (Beijing), “The modification of carbohydrates with fluorine can profoundly affect molecules’ chemical and physical properties such as conformation, lipophilicity, and stability.” In December 2021, they reported the development of a scalable, stereoselective, de novo synthesis  of C2-fluorinated Digitalis-type oligosaccharides, including digoxin.

The key steps in the authors’ synthesis were a Sharpless kinetic resolution and an organocatalytic fluorination of an aldehyde intermediate. The fluorinated digoxin1 was completed in 10 steps after the fluorination reaction.

Molecule of  the Future

It turned out that the fluorinated derivative exhibited ≈10 times less cytotoxicity toward A549 non–small-cell lung cancer cells than original digoxin. This result demonstrated that adding the fluorine atom indeed affected biological activity, which the authors state is worthy of additional research.

1. CAS Reg. No. 2769846-71-9.

Molecule of the Future

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Digoxin fast facts

CAS Reg. No. 20830-75-5
SciFinder
nomenclature
Card-20(22)-enolide, 3-[(O-2,6-dideoxy-β-D-ribo-hexopyranosyl-(1→4)-O-2,6-dideoxy-β-D-ribo-hexopyranosyl-(1→4)-2,6-dideoxy-β-D-ribo-hexopyranosyl) oxy]-12,14-dihydroxy-, (3β,5β,12β)-
Empirical formula C41H64O14
Molar mass 780.94 g/mol
Appearance White crystals or powder
Melting point 230–265 °C (dec.)
Water solubility 65 mg/L
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