Trichothecenes properties

Some natural products, or their degradation products, represent a hazard for mammals not because of general toxicity but for subtle, adverse properties, such as carcinogenicity and tumor promotion. They are best known fi om marine dinoflagellates (okadaic acid and structural analogues), filamentous fungi (trichothecenes and ochratoxins), and plants (pyrrolizidine alkaloids). 

Trichothecene mycotoxins can be delivered as dusts, droplets, aerosols, or smoke from aircraft, rockets, missiles, artillery, mines, or portable sprayers. Because of their antipersonnel properties, ease of large-scale production, and apparent proven delivery by various aerial dispersal systems, the trichothecene mycotoxins (especially T-2 toxin) have an excellent potential for weaponization. 

Studies with radiolabeled trichothecene mycotoxins suggest that the toxin interaction with cells is best viewed as (1) a free, bidirectional movement of these low-molecular-weight chemicals across the plasma membrane and (2) specific, high-affinity binding to ribosomes.51 Thus, further evidence indicates that the primary toxic effects of the trichothecene mycotoxins is caused by their properties as potent inhibitors of protein synthesis. 

C22H32O8, Mr 424.49, light yellow oil. Mycotoxin of the tric(h)othecene group formed by various Fusa-rium species. It is also formed in the metabolism of T-2 toxin. In comparison to the latter, H. is about 3- to 10-times less toxic. Otherwise it exhibits the typical properties of the trichothecenes. LD50 (mouse i.p.) 9mg/kg. 

C24H34O, Mr 466.53, mp. 151 - I52°C, needles, [a] -15.5° (CHClj), a mycotoxin of the tric(h)othecene type formed by Gibberella zeae. various Fusarium species, and Trichoderma lignorum. T. exhibits the typical properties of a trichothecene compound, such as emetic, skin irritating, cytotoxic activities and skin necrosis. LD50 (mouse i. p.) 3 mg/kg. The previously suggested cancerogenic activity was not confirmed. As a... 

Recently, Bayliss et al. [132] described the synthesis of anthracene-9-carbonyl chloride and its aplications as a label for fluorescence and UV absorbance detection of hydroxy compounds. The preparation and properties of esters of short-chain alcohols, diols, trichothecene mycotoxins and sterols were investigated. Anthracene-9-carbonyl chloride was prepared from commercial anthracene-9-carboxylic acid. Derivatization was carried out in acetonitrile free from water or active hydrogen compounds. The reaction rate was dejjendent on the structure of the alcohol. The derivatization of diethylene glycol was complete at ambient temp>erature within 10 min (0.25 M reagent) or 30 min (0.1 M reagent) without a catalyst, but required 1 h for diolesteroL testosterone and the trichothecene T-2 toxin. For sterically hindered alcohols such as t-butanol and 17a-methyl-testosterone, more than 10 h, or refluxing for 1 h, was needed to complete the reaction. The derivatives had absorption maxima at 250 run. Both normal and reversed phase HPLC were applied to the separation of the derivatives. 

For GC the mycotoxins need to be sufficiently thermostable and volatile or be converted into volatile derivatives. The two most widely used detectors in mycotoxin analysis - flame ionization detectors (FIDs) and electron capture detectors (ECDs) - do not require that a compound show any fluorescence or UV absorption, and the group of mycotoxins for which GC was initially the most widely used was that of the trichothecenes. More recently another group of Fusarium mycotoxins, the fumonisins, which also lack the appropriate optical properties, have been analyzed successfully using GC. 

Trichothecenes are responsible for major agricultural losses (Bamburg, 1976 Kamimura et al., 1979 Koroda et al., 1979 Gruber and Paoli, 1980 Mirocha et al., 1981 Schmidt et al., 1981 a,b Scott et al., 1981 Watson and Lindsay, 1982). They may have been used as biological warfare agents (Marshall, 1982 Kucewich, 1982). These observations suggest that basic and applied studies are need to find ways to inactivate the toxic properties of trichothecenes, both in the pure state and in foods and feeds. Such inactivation should lead to better and safer... 

Biological effects of trichothecenes depend on their structural integrity. Previous studies (Bamburg, 1976) have shown that opening the epoxide ring(s) present in all trichothecene molecules essentially abolishes their toxic properties. Modification... 

A variety of biologically active compounds that contain structural features present In trichothecenes readily combine with thiols both in vitro and Iji vivo. Therefore, trichothecenes probably will behave similarly. My hypothesis Is that the double bond of nllvalenol and other 8-ketotr1chothecenes will combine readily with thiols and related compounds under appropriate conditions of pH and temperature leading to major changes In toxicological properties of trichothecenes (Figure 91. 

Chemical characteristics. Trichothecenes belong to a class of sesquiterpene iactones known as 12,13-epoxytrichothecenes. Toxicological properties depend, in part, on the presence of a 12,13 epoxy group loss of the epoxide function markedly reduces toxicity. 

The macrocyclic ester derivatives of trichothecene alcohols (Figs. 7 and 8) possess remarkable biological properties. Verrucarin A (32) was the first member of this group whose structure was established by the extensive use of chemical and spectroscopic methods (Gutzwiller and Tamm, 1965a Tamm and Gutzwiller, 1962). The structure was then confirmed by an X-ray analysis... 

---