Search

The present study describes the synthesis and anti-amoebic activity of 4,6-disubstituted aminopyrimidines (1b–10b) and their sulphonamide derivatives (1–20). All the desired compounds were characterized by spectral data and their purity was confirmed by elemental analysis. The aim of the study was to explore the effect of the target compounds on in vitro growth of HM1:IMSS strain of Entamoeba histolytica. In vitro anti-amoebic activity was performed by microdilution method and the results were compared with standard drug metronidazole. The results revealed that sulphonamide derivatives (1–20) showed better activity than 4,6-disubstituted aminopyrimidines (1b–10b). 5 pyrimidine and 12 sulphonamide derivatives were better inhibitors of the growth of E. histolytica than the reference drug metronidazole (IC50 = 1.80 μM). The promising in vitro anti-amoebic activity of the compounds make them promising molecules for further lead optimization in the development of novel anti-amoebic agents, therefore, it is hoped that these preliminary results could help in designing better molecules with an enhanced anti-amoebic activity.

In the quest for potent anti-amoebic agents, some 1,3,4-thiadiazole derivatives were synthesized and characterized by spectral data. The purity of the compounds was confirmed by elemental analysis. All the compounds were screened in vitro against HM1:IMSS strain of Entamoeba histolytica by microdilution method. The results revealed that compounds 1 (IC50 = 0.670 μM), 3 (IC50 = 1.60 μM) and 8 (IC50 = 0.522 μM) had much better anti-amoebic activity than the reference drug metronidazole (IC50 = 1.80 μM). Further, cytotoxicity of the compounds having IC50 value less than metronidazole was assessed by MTT assay on human breast cancer MCF-7 cell line and all the compounds were found low cytotoxic in the concentration range of 2.5–250 μM. Preliminary results indicate that these three compounds (1, 3 and 8) may be subjected to further investigations and it may be hoped that the present study will stimulate efforts towards the development of novel effective anti-amoebic agents.

Mannich base derivatives of 5-(pyridine-4-yl)-1,3,4-oxadiazole-2-(3H)-thione with substituted piperazine were synthesized and characterized. In vitro antiamoebic activity was performed against HM1: IMSS strain of Entamoeba histolytica and the cytotoxicity of the compounds having IC50 value less than metronidazole was assessed by MTT assay on human breast cancer MCF-7 cell line. The results revealed that compounds 2, 3 and 5 were found to be better inhibitors of E. histolytica than the reference drug metronidazole and found low cytotoxic in the concentration range of 2.5–250 μM. This study suggests the possibility of developing 1,3,4-oxadiazole analogues as potential drug candidates.

Pyrazolo[3,4-d]pyrimidine analogues were synthesized by treating 3-phenyl-1H-pyrazolo[3,4-d]pyrimidine-4-amine with different sulfonyl chlorides and triethylamine in dry dichloromethane. The structure of all the compounds was elucidated by spectral data and their purity was confirmed by elemental analysis. In vitro antiamoebic activity was performed against HM1:IMSS strain of Entamoeba histolytica and two compounds, 4 (IC50 = 0.57) and 6 (IC50 = 0.68), were found better inhibitors than the reference drug metronidazole (IC50 = 1.80). Further, both the compounds (4 and 6) were low cytotoxic against the human breast cancer MCF-7 cell line in the concentration range of 2.5–250 μM. These preliminary results reveal that pyrazolo[3,4-d]pyrimidine analogues could help in designing better molecules with enhanced antiamoebic activity.