Trypanocidal activity

One of the most compelling targets in the polyamine biosynthesis pathway has been S-adenosylmethionine decarboxylase (SAM-DC). This target was chemically validated with the discovery of trypanocidal activity of MDL-73811 nearly two decades ago. Work to understand the unique kinetics for inhibition of this enzyme in T. brucei has shown that a catalytically... 

The nitric oxide donor SIN-1 13 (Section 5.03.12) reacts with 4-nitrophenyl chloroformate to give the N-acylated product that also acts as a potent nitric oxide donor. Further derivatives with trypanocidal activities may be prepared by transesterification with various alcohols <2003JHC943>. 

Trypanocidal activity of phenanthridine derivatives was discovered in 1938 when phenidium (71) was tested versus T. congolense in mice. Dimidium (72) was quickly found more efficacious when both compounds were introduced for field use. However, for cattle, dimidium (72) is a relatively toxic substance. The discovery that homidium (73) is 10 to 50 times more potent as a trypanocide as well as less toxic to the host led to its introduction and continued use at a dose level of 1 mg kg-1. 

Quinapyramine (74) has a broader spectrum of trypanocidal activity than the phenanthridine drugs and is less toxic. A dose of 4.4 mg kg-1 is curative in cattle infected with T. vivax and T. congolense. 

In early Modem Times, the history of HAT was closely linked to the slave trade [14]. The trypanocidal activity of arsenic was discovered fortuitously by Sir David Linvingstone (1813-1873). He relates in Arsenic as remedy for the tsetse bite that the idea occurred in his mind about the year 1847-1848 [15]. Sir Livingstone tried the remedy on horses (two grains of arsenic) but 2 months after an apparent cure, the mare became like a skeleton and he saw her at last perish through sheer exhaustion. Subsequently, better results were obtained with organoarsenical dmgs (Table 1). 

The first significant organoarsenical dmg was synthesized by Pierre Antoine Bechamp (1816-1908) by chemically reacting arsenic acid with aniline [16,17]. Bechamp isolated a colorless compound that he regarded as an anilide of arsenic acid (Fig. 2a). Some 40 years after its initial synthesis, Wolferstan Thomas in Liverpool demonstrated the trypanocidal activity of atoxyl [18] and a few years later it was also used in the treatment of syphilis [19]. Hence, Bechamp s anilide began to be used to treat disease. At the same time, Ferdinand Blumenthal described... 

Loiseau PM, Lubert P, Wolf JG (2000) Contribution of dithiol ligands to In vitro and In vivo trypanocidal activities of dithiaarsanes and investigation of ligand exchange in an aqueous solution. Antimicrob Agents Chemother 44 2954—2961... 

Because of such extensive application in folk medicine, it is easy to understand the interest that the lapachol, the related naphthoquinones a-lapachone, P-lapachone and other naphthoquinones derivatives, have aroused as potential drugs. In fact, a broad variety of biological activities have been described for this kind of compounds. Some examples are antitumor promoting activities [11-12], inactivators of human cytomegalovirus protease [13], antiprotozoal activity [14], trypanocidal activity [15], anticancer activity [16], and antibacterial and antifungal activities [17]. 

An application of this methodology to the synthesis of several tetrahydrofuran lignan derivatives having trypanocidal activity was further reported by Kato and co-workers [62]. This sequential palladium-mediated Michael... 

A number of indoxazenes show physiological activity and have been tested for pharmacological use. Some 4,5,6,7-tetrahydro derivatives, for instance, were tried as analeptics.94 Compounds such as 61 show trypanocidal activity,63 while derivatives of 6-acetamidoindoxazene-... 

Friedlander synthesis, 2, 444 Quinalphos as insecticide, 1, 196 Quinapyramine trypanocidal activity veterinary use, 1, 215 Quinazolinamines structure, 3, 67 1,2,4-triazoIes from, 5, 779 Quinazolin-4-amines sulfonylation, 3, 86 Quinazoline, 2-alkoxy-Hilbert-Johnson reaction, 3, 93 Quinazoline, 4-alkoxy-Hilbert-Johnson reaction, 3, 93 Quinazoline, 6-alkoxy-Hilbert-Johnson reaction, 3, 93 Quinazoline, 4-alkyl-synthesis, 3, 124 Quinazoline, 2-alkyIthio-synthesis, 3, 137 Quinazoline, 4-alkyIthio-synthesis, 3, 137... 

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