Antischistosomal agents

Lucanthone (20) constitutes one of the first effective antischistosomal agents. Biological investigation of this agent showed that the active species in man is in fact the hydroxylated metabolic product hycanthone (21). The published Synthesis for the... 

Drescher, K.M., Rogers, E.J., Bruce, J.I., Katz, N., Dias, L.C. and Coles, G.C. (1993) Response of drug resistant isolates of Schistosoma mansoni to antischistosomal agents. Memorias do Instituto Oswaldo Cruz 88, 89-95. 

Gonnert, R. and Andrews, P. (1977) Praziquantel, a new board-spectrum antischistosomal agent. Zeitschrift fur Parasitenkund 52, 129-1 50. 

Stibamine glucoside [ban, inn] is an antimonal ANTIPROTOZOAL, formerly used for leishmaniasis, stibocaptate [ban] (sodium stibocaptate [inn]) is an antimonal ANTISCHISTOSOMAL AGENT. 

Oltipraz [4-methyl-5-(2-pyrazinyl)-l, 2-dithiole-3-thione] (OPZ), a synthetic derivative of 1, 2-dithiole-3-thione, has been extensively investigated for its chemopreventive properties first developed as an antischistosomal agent, this compound was found to increase cellular thiol levels and to induce enzymes involved in the maintenance of reduced glutathione (GSH) pools and in detoxification of electrophilic intermediates. Induction of phase 2 enzymes such as GSTs, epoxide hydrolases, and NADP(H) quinone reductases was considered to represent the key mechanism of chemoprotection of OPZ. More recently this compound was also found to modulate phase 1 enzymes, antioxidant enzymes, and other inactivating proteins, thereby indicating that its chemoprevention mechanism(s) are more complex than first envisaged. In this chapter, current information about the effects of OPZ on phase 1 and phase 2 enzymes is presented. 

Figure 20 Praziquantel and cyclic nucleoside phosphonates as antischistosomal agents.

Fluorinated 1,2,5-oxadiazoles have also been considered as important fragments in the field of medicinal chemistry, but only very recently compounds with considerable activity have been discovered. Some fluoroaryl substituted furoxans derivatives (Fig. 7), developed in the frame of SAR studies on Furoxan, were reported as inhibitors of thioredoxin glutathione reductase (TGR), with nitric oxide (NO) donor ability, acting as efficacious antischistosomal agents [119]. In particular, compounds 238 and 239 displayed an inhibition activity comparable to that of lead compound. 

Abstracts of Papers, Conference on the Pharmacological and Chemotherapeutic Properties of Niridazole and other Antischistosomal Agents, under the auspices of the New York Academy of Sciences, October 10-13, 1967. 

Oltipraz s—s, N. f Jl 4 CH3 N 1,2-dithiol e-3-thione Antischistosomal drug and cancer chemopreventive agent... 

In 1955, Cuckler and coworkers [23] demonstrated the antischistosomal activity of 2-acetamido-5-nitrothiazole (14) this compound was found to be marginally effective in reducing the schistosome population when given at a concentration of 0.1-0.4% in diet. A major breakthrough was achieved when Ciba laboratories undertook an extensive search for potential antibacterial and/or antiparasitic agents derived from nitroheterocycles. In 1964, Lambert et al. [24,25] announced the discovery of niridazole (15) as a novel drug for the treatment of schistosomiasis. 

Uses Antibacterial agent to treat blackhead disease in turkeys and chickens to treat trichomoniasis in pigeons in synthesis of another antiprotozoal agent, nithiazide to make the antischistosomal drug, nindazole... 

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