Studies on the reactivity of fused thiazole toward nucleophilic reagents: Synthesis of new thiazolo‐derivatives of potential antischistosomal activity

Abstract

AbstractSchistosomiasis is considered one of the most important human helminth infection in terms of morbidity and infectivity (Chitsulo et al. Acta Trop 2000, 77, 41; Engles et al. Acta Trop 2002, 82, 139; Shelly et al. Mol Biochem Parasitol 1993, 60, 93). Derivatives of 2‐amino‐5‐nitrothiazoles have shown activity against Schistosoma mansoni (S. mansoni) and Schistosoma haematobium (S. haematobium), but due to their toxic effect we synthesized new derivatives of a heteroaromatic amine with thiazole moiety. Required thiazole derivatives were prepared via 1 and 2. In this work, two batches of animals were used to test the efficacy of 10 derivatives of thiazole against schistosomiasis. The first batch of Swiss albino mice was infected with S. mansoni and was treated with 5 × 50 mg/kg b.w. The second batch of golden hamsters was infected with S. haematobium and was treated with 5 × 100 mg/kg b.w. Parasitological parameters, biochemical studies, and granuloma diameter were estimated. Results indicated that in the case of S. mansoni infected mice, compounds 2 (2‐amino‐4‐thiazoliniminium chloride) and 20 (2,4‐diamino thiazole) showed moderate efficacy (50% worm reduction). While compounds 18 (4‐dicyanomethylene‐4, 5‐dihydrothiazo‐2‐yl)‐N,N‐dimethylimidoformamide) and 21 2‐(dimethylamino) methylene‐1,3‐thiazol‐4‐yl)‐N,N‐dimethylimidoformamide) showed 83% and 90% worm reduction with some normalization of liver function and significant reduction in hepatic granuloma diameters. In the case of S. haematobium infected hamsters, compound 15 showed reduction of worms by about 50% with improvement in kidney function. The high effect of compounds 18 and 21 compared to 2, 15, and 20 could be attributed to the dimethylimidoformamide moieties combined with the thiazole ring. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:121–222, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20072