Diallyl trisulfide

Diallyl trisulfide
Names
IUPAC name
3-(prop-2-enyltrisulfanyl)prop-1-ene
Other names
Allitridin
Identifiers
2050-87-5
3D model (Jmol) Interactive image
ChEBI CHEBI:78492
ChemSpider 15481
ECHA InfoCard 100.016.462
EC Number 218-107-8
PubChem 16315
Properties
C6H10S3
Molar mass 178.33 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Diallyl trisulfide (DATS), also known as Allitridin, is an organosulfur compound with the formula S(SCH2CH=CH2)2. It is one of several produced by the hydrolysis of allicin, including diallyl disulfide and diallyl tetrasulfide, DATS is one of the most potent.[1]

Biological applications

Many health benefits of garlic are attributed in part to DATS. These benefits include anti-cancer effects, platelet aggregation, blood pressure reduction, decreases in cholesterol levels, and increases in levels of reactive oxygen species.[2] DATS has been shown to selectively kill cancerous cells in the prostate and breast,[3][4] 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 activity.[5] These effects appear to contribute to the apoptosis of cancer cells and a decrease in cancer cell proliferation.

DATS can be metabolized by glutathione in red blood cells to form hydrogen sulfide (H2S).[2] This conversion occurs at a consistent rate over a prolonged period of time, rendering DATS a good source of H2S.[6] H2S is a cardioprotective agent that has antioxidant, anti-inflammatory, and anti-apoptotic effects,.[6][7] 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.[6] 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).[6] 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,.[2][8] This causes vasodilation and improves hemodynamics.[2]

DATS is a promising treatment for cardiac arrhythmias 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.[9] 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.[10] This decreases the amount of functional potassium ion rectifier channels on the cell membrane and thus, slows depolarization.[10] However, hERG trafficking impairment has also been shown to cause arrhythmias due to the development of long QT syndrome and should be considered in drug development.[10]

References

  1. ↑ Block. E (2010) Garlic and Other Alliums: The Lore and the Science. Retrieved from https://books.google.com/books?id=6AB89RHV9ucC
  2. 1 2 3 4 Benavides, G., Squadrito, G., Mills, R., Patel, H., Isbell, T., Patel, R., Darley-Usmar, V., Doeller, J., Kraus, D. (2007) Hydrogen Sulfide Mediates the Vasoactivity of Garlic. Proceedings of the National Academy of Sciences of the United States of America, volume 104, 17977-17982,
  3. ↑ Hye-Kyung, N., Eun-Hee, K., Min-Ah, C., Jong-Min, P., Do-Hee, K., Young-Joon, S. (2012) Diallyl Trisulfide Induces Apoptosis in Human Breast Cancer Cells Through ROS-Mediated Activation of JNK and AP-1. Biochemical Pharmacology, 84 (10): 1241-1250
  4. ↑ Ixao, D., Singh, S. (2006) Diallyl Trisulfide, a Constituent of Processed Garlic, Inactivates Akt to Trigger Mitochondrial Translocation of BAD and Capase-Mediated Apoptosis in Human Prostate Cancer Cells. Carcinogenesis, 27 (3): 533-540
  5. ↑ Seki, T., Hosono, T., Hosono-Fukao, T., Inada, K., Tanaka, R., Ogihara, J., Ariga, T. (2008) Anticancer Effects of Diallyl Trisulfide Derived from Garlic. Asia Pacific Journal of Clinical Nutrition, 1: 249-252
  6. 1 2 3 4 Predmore, B., Kondo, K., Bhushan, S., Zlatopolsky, M., King, A., Aragon, J., Grinsfelder, B., Condit, M., Lefer, D. (2012) The Polysulfide Diallyl Trisulfide Protects the Ischemic Myocardium by Preservation of Endogenous Hydrogen Sulfide and Increasing the Nitric Oxide Bioavaiblility. American Journal of Physiology – Heart and Circulatory Physiology, 302 (11): H2410-2418
  7. ↑ Lavu, M., Bhushan, S., Lefer, D. (2011) Hydrogen Sulfide-Mediated Cardioprotection: Mechanism and Therapeutic Potential. Clinical Science London, 120 (6): 219-229
  8. ↑ Weerateerandkul, P., Chattipakorn, S., Chattipakorn, N. (2011) Roles of the Nitric Oxide Signaling Pathway in Cardiac Ischemic Preconditioning Against Myocardial Ischemia-reperfusion Injury. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 17 (2): 44-52
  9. ↑ Vandenberg, J., Perry, M., Perrin, M., Mann, S., Ke, Y., Hill, A. (2012) hERG K(+) Channels: Structure, Function, and Clinical Significance. Physiology Review, 92 (3): 1393-1478
  10. 1 2 3 Li, G., Cheng, G., Wu, J., Ma, S., Zhang, A., Han, W., Sun, C. (2014) Allitridin reduces IKr Current by Disrupting the Trafficking of Human Ether-à-go-go-Related Gene Channels. Cardiology, 128: 1-8
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