Gramine – fighting natural toxins with natural toxins

Gramine (N,N-Dimethyl-3-aminomethylindole, CAS 87-52-5) is an important allelochemical mainly produced by plant species of the genus Lupinus (Fabaceae), Hordeum and Phalaris (both Poaceae). It is one of the major alkaloids found in yellow lupins (Lupinus luteus) where it can make up 64-94% of the plants total alkaloid content. The plants yellow seeds are still consumed as a delicacy in the form of pickled lupin beans. Other plants producing gramine include widely occurring grass species such as the important cereal grain barley (Hordeum vulgare) or those of the genus Phalaris, often found in wetlands or riparian habitats.

The strong base gramine (pK_a=8.99, ChemAxon) can be categorized as mobile (log K_oc=3.6, EPISuite) and persistent (total persistence time 46 days, EPISuite) in the aquatic environment. Considering the toxins intrinsic properties and widespread occurrence, gramine could potentially be found in surface waters adjacent to agricultural fields or in wetlands.

Gramine is known to generally show weak inhibition of the acetylcholine esterase, causing vasodilating effects or kidney damage in mice. The phytotoxin also presents inhibitory effects on the growth of other plants or bacteria. As such the allelochemical gramine has been tested as a natural algicide to control blooms of the cyanobacteria Microcystis aeruginosa. It could be demonstrated that the chemical effectively inhibited their growth by increasing the level of reactive oxygen species in the cells and thus causing oxidative stress often lethal for the organism. Applying the phytotoxin gramine to control harmful algal blooms and prevent the production of toxic cyanobacterial metabolites could be another pathway for the compound to reach water resources. Fighting natural toxins with natural toxins as biopesticides could be an interesting alternative to the use of synthetic chemicals. However, fighting one toxin with another also raises many concerns and thus, the use of natural toxins as safe biopesticides still requires a vast amount of research.

SMILES: CN(C)Cc1c[nH]c2c1cccc2

References:

• Teuscher, E.; Lindequist, U. (2010) Biogene Gifte: Biologie-Chemie-Pharmakologie-Toxikologie. Wissenschaftliche Verlagsgesellschaft GmbH, Stuttgart, 3 Auflage.
• Hong et al.; Gramine-induced growth inhibition, oxidative damage and antioxidant responses in freshwater cyanobacterium Microcystis aeruginosa. Aquat. Toxicol. 91, 2008, 262-269.
• ChemSpider, CSID:6625, http://www.chemspider.com/Chemical-Structure.6625.html (accessed 08:42, May 7, 2019)

Pictures:

• https://commons.wikimedia.org/wiki/File:Lupinus_spec_b.JPG#file
• https://commons.wikimedia.org/wiki/File:Horedum_vulgare_(3819804188).jpg
• https://upload.wikimedia.org/wikipedia/commons/e/ea/Cyanobacteria_Aggregation2.jpg