Diallyl trisulfide (DATS), also known as Allitridin, is an

organosulfur compound Organosulfur compounds are organic compounds that contain sulfur. They are often associated with foul odors, but many of the sweetest compounds known are organosulfur derivatives, e.g., saccharin. Nature abounds with organosulfur compounds—sulfu ...

with the formula S(SCH₂CH=CH₂)₂. It is one of several produced by the hydrolysis of

allicin Allicin is an organosulfur compound obtained from garlic, a species in the family Alliaceae. It was first isolated and studied in the laboratory by Chester J. Cavallito and John Hays Bailey in 1944. When fresh garlic is chopped or crushed, the ...

, including

diallyl disulfide Diallyl disulfide (DADS or 4,5-dithia-1,7-octadiene) is an organosulfur compound derived from garlic and a few other genus ''Allium'' plants. Along with diallyl trisulfide and diallyl tetrasulfide, it is one of the principal components of the dis ...

and diallyl tetrasulfide, DATS is one of the most potent.

Biological applications

DATS has been shown to selectively kill cancerous cells in the prostate and breast, leaving healthy cells unharmed. This effect is attributed to increased reactive oxygen species (ROS) within cancer cells, increased the number of cells that arrest in the G2 phase of mitosis, and promote an increase in

caspase-3 Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the ''CASP3'' gene. ''CASP3'' orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also p ...

activity. These effects appear to contribute to the

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

of cancer cells and a decrease in cancer cell proliferation. DATS can be metabolized by

glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pero ...

in red blood cells to form

hydrogen sulfide Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is poisonous, corrosive, and flammable, with trace amounts in ambient atmosphere having a characteristic foul odor of rotten eggs. The unde ...

(H2S). This conversion occurs at a consistent rate over a prolonged period of time, rendering DATS a good source of H2S. H2S is a cardioprotective agent that has antioxidant, anti-inflammatory, and anti-apoptotic effects,. A major topic of research is the impact of hydrogen sulfide on reducing myocardial ischemia-reperfusion injury. Reperfusion injury is a significant threat to myocardial function that arises with the reintroduction of blood flow to the heart following an ischemic episode. Reperfusion triggers an inflammatory response and often results in oxidative damage. H2S decreases injury through many different effects such a decrease in oxidative stress, maintenance of mitochondrial function, and increased eNOS (endothelial nitric oxide synthase) activation. eNOS is activated via phosphorylation by H2S through the activation of the PI3K/Akt pathway, which increases the formation and bioavailability of nitric oxide (NO). This negatively impacts mitochondria functionality. The mitochondria has been known to protect the heart from ischemic-reperfusion injury through the opening of the ATP-sensitive K+ channel,. This causes vasodilation and improves

hemodynamics Hemodynamics or haemodynamics are the dynamics of blood flow. The circulatory system is controlled by homeostatic mechanisms of autoregulation, just as hydraulic circuits are controlled by control systems. The hemodynamic response continuously mo ...

. DATS is a promising treatment for

cardiac arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

s through its ability to change the opening of the human ether-à-go-go-related (hERG) channel. hERG is the pore-forming subunit of potassium channels that create delayed rectifier potassium ion currents in many cells, including cardiac myocytes. The delayed rectifier potassium ion current is largely responsible for the repolarization of ventricular cardiac myocytes by permitting potassium efflux. DATS causes a decrease in the steady-state inactivation, alters deactivation, and impairs trafficking of the hERG channel from the endoplasmic reticulum to the plasma membrane of the cell. This decreases the amount of functional potassium ion rectifier channels on the cell membrane and thus, slows depolarization. However, hERG trafficking impairment has also been shown to cause arrhythmias due to the development of

long QT syndrome Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainting, d ...

and should be considered in drug development.

References

{{Allium Organosulfur compounds