Agaritina is a natural substance, an amphipathic molecule (it has both a hydrophobic and a hydrophilic group) and a genotoxin that is found in many woodland mushrooms of the species Agaricus, the champignon mushroom and particularly in Agaricus blazei Murrill. It is a hydrazine derivative and has been the subject of research due to its potential health implications.

This compound is a derivative of the amino acid glutamic acid and the amine phenylhydrazine.

• Glutamic acid. It is an amino acid, one of the building blocks of proteins. It plays a key role in cell metabolism and is also the precursor of the neurotransmitter glutamate. It has a carboxyl group (-COOH) and an amine group (-NH2) attached to a carbon atom, as well as a side chain that also contains a carboxyl group.
• Phenylhydrazine. This is an organic compound consisting of a phenyl group (a ring of six carbon atoms, also known as a benzene ring) attached to a hydrazine group (-NH-NH2). Phenylhydrazine is derived from hydrazine and is used in chemical synthesis, particularly in the synthesis of indoles and hydrazones.

The synthesis process takes place in different steps:

• Formation of the phenylhydrazine derivative. Phenylhydrazine is modified to form a derivative that can further react to produce agaritin. This modification step may involve functionalisation of the phenylhydrazine molecule through reactions such as acylation, alkylation or other chemical transformations.
• Glycosylation. The modified phenylhydrazine derivative then undergoes glycosylation, in which a sugar moiety is attached to the molecule. This step is usually achieved by reacting the modified phenylhydrazine with a suitable sugar or sugar derivative.
• Purification. The crude product obtained from the glycosylation step is usually impure and contains other by-products. Purification techniques such as column chromatography, crystallisation or recrystallisation can be used to isolate agaritin from impurities.
• Characterisation and analysis. Once purified, the synthesised agaritin must be characterised and analysed to confirm its chemical structure and purity. Techniques such as nuclear magnetic resonance (NMR), mass spectrometry (MS) and infrared spectroscopy (IR) can be used for structural analysis.

Agaritine is typically obtained as a white or off-white crystalline solid.

What it is used for and where

Medical

Agaritine that is present in Agaricus blazei, moderately induces apoptosis in U937 leukemia cells (1), and may be considered an attractive candidate for the development of anti-HIV drugs (2). Beta-glucans, a class of polysaccharide fibers found in these fungi belonging to the family Basidiomycetes, have also been shown to act as immunostimulants against cancer cells (3).

The most relevant studies have been selected for this chemical compound with a summary of their contents:

Agaritine studies

• Molecular Formula: C₁₂H₁₇N₃O₄ 
• Molecular Weight: 267.285 g/mol
• CAS: 2757-90-6
• EC Number: 
• UNII: UX8Y7QVP8M

Synonyms: 

• beta-N-(gamma-L(+)Glutamyl)4-hydroxymethylphenylhydrazine
• L-Glutamic acid, 5-(2-(4-(hydroxymethyl)phenyl)hydrazide)
• Glutamic acid, 5-(2-(alpha-hydroxy-p-tolyl)hydrazide), L-
• beta-N-[gamma-l(+)-Glutamyl]-4-hydroxymethylphenylhydrazine
• L-Glutamic acid, 5-(2-(alpha-hydroxy-para-tolyl)hydrazide)
• L-Glutamic acid, 5-(2-(4-(hydroxymethyl)phenyl)hydrazide) (9CI)
• 2-[4-(hydroxymethyl)phenyl]-L-glutamohydrazide
• (2S)-2-amino-5-{2-[4-(hydroxymethyl)phenyl]hydrazino}-5-oxopentanoic acid
• beta-N-(alpha-L-Glutamyl)-4-hydroxymethylphenylhydrazine
• L-Glutamic acid,5-[2-[4-(hydroxymethyl)phenyl]hydrazide]
• 2-amino-5-{2-[4-(hydroxymethyl)phenyl]hydrazino}-5-oxopentanoic acid

References__________________________________________________________

(1) Akiyama H, Endo M, Matsui T, Katsuda I, Emi N, Kawamoto Y, Koike T, Beppu H. Agaritine from Agaricus blazei Murrill induces apoptosis in the leukemic cell line U937. Biochim Biophys Acta. 2011 May;1810(5):519-25. doi: 10.1016/j.bbagen.2011.02.010. 

Endo M, Beppu H, Akiyama H, Wakamatsu K, Ito S, Kawamoto Y, Shimpo K, Sumiya T, Koike T, Matsui T. Agaritine purified from Agaricus blazei Murrill exerts anti-tumor activity against leukemic cells. Biochim Biophys Acta. 2010 Jul;1800(7):669-73. doi: 10.1016/j.bbagen.2010.03.016. 

(2) Gao WN, Wei DQ, Li Y, Gao H, Xu WR, Li AX, Chou KC. Agaritine and its derivatives are potential inhibitors against HIV proteases. Med Chem. 2007 May;3(3):221-6. doi: 10.2174/157340607780620644. 

Abstract. Agaritine, or beta-N-[gamma-L(+)-glutamyl]-4-hydroxymethylphenylhydrazine, is a Chinese herbal medicine, known having the antiviral and anticancer function. However, so far no reports whatsoever have been made for its potential as an anti-HIV agent. It was observed by docking experiments for more than 9,000 compounds extracted from various Chinese medicines that the compound agaritine distinguished itself from all the others in binding to the HIV protease with the most favorable free energy. Based on this, a series of derivatives were generated by modifying agaritine. It has been observed thru an extensive docking study that some of agaritine derivatives had markedly stronger binding interaction with the HIV protease than agaritine, suggesting that these derivatives might be good candidates for developing drugs for AIDS therapy.

(3) Bashir KMI, Choi JS. Clinical and Physiological Perspectives of β-Glucans: The Past, Present, and Future. Int J Mol Sci. 2017 Sep 5;18(9):1906. doi: 10.3390/ijms18091906. 

Abstract. β-Glucans are a group of biologically-active fibers or polysaccharides from natural sources with proven medical significance. β-Glucans are known to have antitumor, anti-inflammatory, anti-obesity, anti-allergic, anti-osteoporotic, and immunomodulating activities. β-Glucans are natural bioactive compounds and can be taken orally, as a food supplement, or as part of a daily diet, and are considered safe to use. The medical significance and efficiency of β-glucans are confirmed in vitro, as well as using animal- and human-based clinical studies. However, systematic study on the clinical and physiological significance of β-glucans is scarce. In this review, we not only discuss the clinical and physiological importance of β-glucans, we also compare their biological activities through the existing in vitro and animal-based in vivo studies. This review provides extensive data on the clinical study of β-glucans.