Mechanism of Action and Biological Activities of Dimethyl Disulfide

Dimethyl disulfide (DMDS) is known to exhibit a wide range of biological activities, which can be attributed to its various mechanisms of action. One of the primary mechanisms is its ability to interact with and inhibit the activity of certain enzymes, particularly those involved in oxidative processes.

Enzyme Inhibition and Redox Regulation

DMDS has been shown to inhibit the activity of enzymes such as glutathione reductase, which plays a crucial role in maintaining cellular redox balance [1]. Glutathione reductase is responsible for converting oxidized glutathione (GSSG) into its reduced form (GSH), a process that is essential for the regulation of cellular oxidative stress and the maintenance of the appropriate redox state within the cell.[2]

DMDS is believed to inhibit glutathione reductase by interacting with the enzyme’s active site, possibly through the formation of a reversible covalent adduct between the sulfur atoms of the disulfide moiety and the thiol groups of the enzyme’s cysteine residues.[3] This inhibition of glutathione reductase can lead to an imbalance in the cellular redox status, resulting in increased oxidative stress and the potential for various downstream effects on cellular function and signaling pathways.

Antimicrobial Activity

In addition to its effects on enzymatic processes, DMDS has also been reported to possess antimicrobial properties, inhibiting the growth of various bacteria, fungi, and even some viruses. [4]The proposed mechanism for this antimicrobial activity is related to the compound’s ability to disrupt cell membranes and interfere with essential cellular processes.

DMDS is thought to interact with the lipid bilayer of microbial cell membranes, altering their permeability and potentially leading to the leakage of critical cellular components[5]. This disruption of the cell membrane can also impair other cellular processes, such as respiration.

References

1. Mosca, N., Petrillo, S., Bortolani, S., Monforte, M., Ricci, E., Piemonte, F., & Tasca, G. (2021). Redox homeostasis in muscular dystrophies. Cells, 10(6), 1364, Redox homeostasis in muscular dystrophies.(2021).
2. Raj Rai, S., Bhattacharyya, C., Sarkar, A., Chakraborty, S., Sircar, E., Dutta, S., & Sengupta, R. (2021). Glutathione: Role in oxidative/nitrosative stress, antioxidant defense, and treatments. ChemistrySelect, 6(18), 4566-4590., : Role in oxidative/nitrosative stress, antioxidant defense, and treatments. .(2021).
3. Kumagai, Y., & Abiko, Y. (2017). Environmental electrophiles: protein adducts, modulation of redox signaling, and interaction with persulfides/polysulfides. Chemical Research in Toxicology, 30(1), 203-219.,Environmental electrophiles: protein adducts, modulation of redox signaling, and interaction with persulfides/polysulfides. .(2017).
4. Santoyo, G., Urtis-Flores, C. A., Loeza-Lara, P. D., Orozco-Mosqueda, M. D. C., & Glick, B. R. (2021). Rhizosphere colonization determinants by plant growth-promoting rhizobacteria (PGPR). Biology, 10(6), 475., Rhizosphere colonization determinants by plant growth-promoting rhizobacteria (PGPR). .(2021).
5. Copolovici, D.M., Langel, K., Eriste, E., & Langel, U. (2014). Cell-penetrating peptides: design, synthesis, and applications. ACS nano, 8(3), 1972-1994., Cell-penetrating peptides: design, synthesis, and applications.(2014).