ABSTRACT
Therapeutic strategy has included diverse pharmaceutical agents of traditional use such as metronidazole, quinacrine, furazolidone and paramomycin, other drugs of more recent introduction, such as albendazole and nitazoxanide, have also been applied as clinical practice. Of these e.g. metronidazole may be considered the most representative anti-giardial agents of traditional and recent use. However, evidence points to an increasing frequency of cases refractory to treatment with these drugs, the causes of which include non-compliance to treatment and emergence of drug resistant Giardia. The aim of this study is to evaluate the therapeutic effect of four new compounds, 3- / [[2E]-3-[dimethylamino] Prop-2-enoyl/ ] -5, 6-diphenyl- 1, 2, 4-triazin-3 [2H]-one [T1] 3-/ [[2E]-3-[dimethylamino] prop2-enoyl]-2H-chromen-2-one [C1] and 3-[Hexa-2, 4 dienoyl]- 4 hydroxy-1-methyl quinolin-2 [1H]-one [Q1] and N, N-Bis / [2,4-dioxo-1-methyl-1, 2, 3, 4-tetrhydroquinol-3y1] methy1/ ] benzidine [Q2] on the infection with Giardia lamblia. Treatment of Giardiasis 2 weeks post-infection with compound T1, C1, orally administered gave a very highly significant reduction in the number of cysts/gm stool were the percentage reduction rate reported for compound T1 given in a dose of [100 and 60 mg/kg] was 94.3% and 83.8%] respectively. However groups treated with compound C1 given in a dose of [100mg/kg and 60mg/kg] resulted 96.2% and 89.1%. When Q1 and Q2, were administered orally a significant reduction in the number of cysts/gm stool was noticed. Percent reduction reported for compound Q1 given in a dose [80 and 60mg/kg] was 89.6% and 72.6% respectively. Representing a highly significant reduction in number of cysts/ gm stool. Where in the compound Q2 percent reduction of cysts/ gm stool was 80.35%, 68.9% stool. The effect of compounds T1, C1, Q1, Q2 on the vegetative [Trophozoite] forms in the small intestine of sacrificed hamsters was studied. Compound T1 orally administered in a dose [100 mg/kg and 60 mg/kg] gave a highly significant reduction in the number of trophozoites [96.7% and 91.7%]. However compound C1 resulted to a significant reduction in the number of trophozoites [75.2% and 60.2%]. It was found that in treatment with compound Q1 and Q2 [80mg/kg and 60mg/ kg] the former was much more efficient than the later i.e there is a highly significant difference [94.5%, 96.7%] in case of Q1, Q2 at a dose of 80mg/kg, where as groups treated with 60mg/ kg of Q1 and Q2 showed much less reduction in the number of trophozoites. The curative effect of these compounds almost ranks with metronidazole. Histopathological examination, revealed a profound effect on the structure and function of the intestinal mucosa, villous shortening and a trophy, hypercellularity of the lamina propria due to increase in the number of mononuclear, polymorphonuclear and eosinophilic cells with diffuse loss of brush border microvillus surface area