Abstract
Purpose: To synthesis a series of novel thiazolo pyrimidine derivatives and evaluate them in vitro for their safety and anthelmintic activity against E. multilocularis metacestodes using BALB/c mice.
Methods: A new series of substituted amino thiazole, hydrazinothiazole and thiazolo pyrimidine derivatives (2-6) were synthesized by reaction of compound 1 with potassium isothiocyanate to give the corresponding compound 2, which was used as starting material. The physicochemical characterization of these derivatives was carried out by nuclear magnetic resonance spectroscopy ((HNMR)-H-1) and mass spectroscopy (MS). The purity of the compounds was determined by elemental analysis. Safety and anthelminthic activity of the compounds against E. multilocularis metacestodes was evaluated in vitro by i) viability assessment and relative abundance of 14-3-3 mRNA determination in E. multilocularis metacestodes-suspensions treated with 2, 5 and 10 mu M concentrations of each compound separately. ii) bioassay at 15 weeks post-inoculation of mice by E. multilocularis suspensions-treated with 30 mu M albendazole (ABZ), 10 mu M thiazolopyrimidine derivative 5 (TPYDa) and a combination of both. Liver functions of all mice were tested before mice sacrifice.
Results: TPYDa emerged as the active anthelmintic compound of the series against E. multilocularis metacestodes viability (activity, 60 %) compared with ABZ (activity, 63 %). When TPYDa was combined with ABZ, the activity reached 86 %. No mortality was found and liver function was normal in all mice during the studies.
Conclusion: The compound, TPYDa, can serve as a lead molecule for further development to a clinically useful novel class of anthelmintic agents.