Thiabendazoles

Thiabendazole (Mintezol) is often used in trichinosis and several other types of roundworm infections (see Table 35-5). The anthelmintic mechanism of this drug is not fully understood, but selective inhibition of 

Physical therapists and occupational therapists working with patients who have AIDS will frequently encounter patients taking systemic antifungal and antiprotozoal drugs. The use of these agents is critical in controlling parasitic infections in patients with AIDS and other individuals with a compromised or deficient immune system. 

Brief History. A physical therapist working with a college football team was taping a team member s ankle when he noticed redness and inflammation between the athlete s toes. The athlete reported that the redness and itching had developed within the last few days and was becoming progressively worse. The therapist suspected a cutaneous fungal infection (probably tinea pedis) and reported this information to the team physician. 

Albougy HA, Naidoo S. A systematic review of the management of oral candidiasis associated with HIV/AIDS. SADJ. 2002 57 457-466. 

Allen JE, Liu LX. Immunity to parasitic and fungal infections. In Pier GB, et al, eds. Immunology, 

Thiabendazole s fungicidal properties had already been reported in 1964, but prior to that it had been used as an anthelmintic in human and veterinary medicine. In aqueous solution it is stable, but in mammals it is hydroxylated in the benzene ring by CYP enzymes. 

History. Since 1962 thiabendazole has been used in the medical sector for animals as an anthelminthic. Since then it was used in different areas as a fungistatie agent for use in medicine (since 1964) or in crop protection as a postharvest fungicide. It was from this latter application that thiabendazole came to be adopted for food preservation, where it is still used on a limited scale for preserving citrus fruits and bananas surfaces. 

Benzimidazole, 2-(4-thiazolyl) 2-(4 -Thiazolyl)benzimidazole 2-(Thiazol-4-yl)benzimidazol 2-(4-Thiazolyl)-1 H-benzimidazole 2-(4-Thiazolyl)benzoimidazole 5-(4-Thiazolyl)benzimidazole Amolden HS Chemviron TK 100 Cropasal Drawipas Equizole G 491 Hokustar HP Mertect Mertect  

Health aspects, acute toxicity. In animals thiabendazole is metabolised to 5-hydroxythiabendazole formed by hydroxylation. In humans metabolic products are eliminated with the urine. 

LD50 oral of thiabendazole for mice, rats and rabbits moves between 3.1 and 3.8g/kg body weight. With dosages above 800mg/kg body weight, growth disturbances occur and the mortality rate increases. 

The ADI-level for thiabendazole is set (by the Joint expert committees of the WHO/FAO) to 0-0.3 mg/kg body weight/day. 

Therapeutic Function Anthelmintic Chemical Name 2-(4-thiazolyl)-1 H-benzimidazole Common Name -Structural Formula  

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Microtubulin Polymerization Inhibitors. The ben2imida2oles were first reported to have systemic fungicidal activity in 1964 (29). Prominent examples include thiabendazole [148-79-8] (42) fuberida2ole [3878-19-1] (43) carbendazim [10605-21-7] (44) benomyl [17804-35-2] (45) and thiophanate methyl [23564-05-8] (46). Benomyl (45), the most widely used member of this group is almost certainly inactive as a fungicide until it is converted in plants and soil to carbendazim (44). Likewise, thiophanate and thiophanate methyl (46) are nonfungitoxic until converted to carbendazin (44). 

Spray solution Thiabendazole Make up 3 ml 30% hydrogen peroxide to 100 ml with 10% acetic acid [2],... 

Changing the substitution pattern on the benzimidazole greatly alters the biologic activity. Thus, inclusion of a thia-zole ring affords thiabendazole (70), a drug used for the treatment of helminthiasis. 

Intermediate arylamidine, 6S, is prepared by the aluminum chloride-catalyzed addition of aniline to the nitrile function of 4-cyanothiazole (67), Amidine, 65, is then converted to its N-chloro analog (69) by means of sodium hypochlorite. On base treatment, this apparently undergoes a nitrene insertion reaction to produce thiabendazole (70), ... 

The exact mechanism of action of thiabendazole (Mintezol) is unknown. This drug appears to suppress egg or larval production and tiierefore may interrupt die life cycle of the helminth. Thiabendazole is used to treat threadworm. Thiabendazole may cause hypersensitivity reactions, drowsiness, and dizziness. 

Thiabendazole is contraindicated in patients with known hypersensitivity. Thiabendazole is used with caution in patients with hepatic or renal disease. Thiabendazole is a Pregnancy Category C drug and is used during pregnancy only if the potential benefit outweighs the risk to the fetus. When thiabendazole is administered with the xanthine derivatives, the plasma level of the xanthine may increase to toxic levels. It is important to monitor xanthine plasma levels closely in case a dosage reduction is necessary. 

Thiabendazole—The patient takes this drug with food to minimize gastrointestinal upset and distress. 

The two examples of sample preparation of solids containing low concentrations of the substances of interest will be the analysis of aflatoxins in corn meal (7) and the determination of the fungicide thiabendazole in citrus fruits. It should be pointed out that the applications chosen in this section attempt to reflect a range of analyses that the analyst is likely to meet in both research and industrial laboratories. 

Chromatogram of Thiabendazole Extracted from Citrus Fruits... 

A method has been reported for the quantification of five fungicides (shown in Figure 5.39) used to control post-harvest decay in citrus fruits to ensure that unacceptable levels of these are not present in fruit entering the food chain [26]. A survey of the literature showed that previously [27] APCl and electrospray ionization (ESI) had been compared for the analysis of ten pesticides, including two of the five of interest, i.e. carbendazim and thiabendazole, and since it was found that APCl was more sensitive for some of these and had direct flow rate compatibility with the HPLC system being used, APCl was chosen as the basis for method development. 

A subsequent comparison of these ionization techniques for the study of another eight pesticides, this time including three of the five of interest [28], i.e. carbendazim, thiabendazole and thiophanate methyl, showed that ESI gave enough sensitivity to allow reliable determination of the pesticides at concentrations below their respective maximum residue levels. 

Thiabendazole Benzimidazole, 2-(4-thiazolyl)- (8) IH-Benzi-midazole, 2-(4-thiazolyl)- (9) (148-79-8)... 

Tetrahydrocannabinol (= THC)-11-carboxylic acid 290 Tetrahydrocortiso 221 Tetrahydrocortisone 221 Tetrahydrosteroids 222 Tetrazolium salts, reduction 61 Thalidomide 45 -, hydrolysis products 45 Thiabendazole 307, 308 Thiamine 235, 236, 397 Thickening agents 179 Thin-layer chromatography, advantage 5 -, numbers of publications per year 6 Thiobarbiturates 45,66 Thiocarbamide derivatives 322 Thiocarbamides, N -ary I-N -benzenesulfo-nyl- 248,249 Thiochrome 395... 

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