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In continuation of our previous work, a series of furan-thiazolidinone hybrids was prepared by Knoevenagel condensation of 3-(furan-2-ylmethyl)-2-(phenylimino)-1, 3-thiazolidin-4-one with different aryl aldehydes in presence of strong base. Some members of the series exhibited remarkable antiamoebic activity and cell viability. Three compounds (3, 6 and 11) showed excellent binding energy for Entamoeba histolytica O-acetyle-l-serine sulfohydrolase and Entamoeba histolytica thioredoxin reductase. These compounds demonstrated significant inhibition of O-acetyle-l-serine sulfohydrolase. The promising antiamoebic activity and enzymatic assay of 3, 6 and 11 make them promising molecules for further lead optimization in the development of novel antiamoebic agents.

Metronidazole hydrazone conjugates (2-13) were synthesized and screened in vitro for antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Six compounds were found to be better inhibitors of E. histolytica than the reference drug metronidazole. These compounds showed greater than 50-60% viability against HeLa cervical cancer cell line after 72 h treatment. Also, molecular docking study was undertaken on E. histolytica thioredoxin reductase (EhTHRase) protein which showed significant binding affinity in the active site. Out of the six actives, some of the compounds showed lipophilic characteristics.

An in-house database of 520 compounds was docked against Entamoeba histolytica thioredoxin reductase (EhTrR), a promising target for the treatment of amoebiasis. Amongst these, some metronidazole (MTZ)-triazole hybrids were ranked high, with docking scores from -10.23 to -7.56. Studies of the binding orientations and conformations show that the head groups of MTZ-triazole hybrids interact with the arginine residues within the binding pocket of EhTrR, making it clear that such is the optimal and most reliable orientation for this class of compounds. The top-ten MTZ-triazole hybrids were then selected for evaluation of their activity against the HM1:IMSS strain of amoeba. The most active compound, 2-pyridyl-(1,2,3-triazolyl)metronidazole 10, with an IC50 value of 8.4 nM, was significantly more active than the standard drug MTZ alone. Docking studies revealed that compound 10 may act as an EhTrR inhibitor with activity in the nanomolar range and satisfactory ADME properties; it is a suitable candidate to be carried forward as a potential lead in the discovery of drugs to combat amoebiasis.

N-Acylhydrazones derived from 7-chloro-4-piperazin-1-yl-quinoline were synthesized and biologically evaluated for blood-stage of Plasmodium falciparum and Entamoeba histolytica trophozoites. N-Acylhydrazone F12 was found to inhibit the P. falciparum growth as well as its life cycle with good selectivity, which was achieved by inhibiting hematin formation. Compound F24 showed better IC50 value than the amoebicidal drug metronidazole.

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.

A series of 1,2,4-triazole derivatives containing thiosemicarbazone linkage was synthesized and evaluated for their in vitro antiamoebic activity against HM1:IMSS strain of Entamoeba histolytica. All the compounds were capable of inhibiting the growth of E. histolytica out of which four compounds (IC(50)=0.28-1.38 μM) were found to have better efficacy than the standard drug Metronidazole (IC(50)=1.8 μM). Cytotoxicity of the active compounds was assessed by MTT assay using human breast cancer MCF-7 cell line, which revealed that all the compounds were low cytotoxic in the concentration range of 2.5-250 μM.

In an effort to develop effective antiamoebic agents, some hydrazones and azoles containing pyridyl moiety were synthesized and screened for in vitro antiamoebic activity against HM1:IMSS strain of Entamoeba histolytica. Among all the compounds, only five compounds (1, 3, 5, 9 and 11) were found to be better inhibitors of growth of E. histolytica than the reference drug metronidazole. The cytotoxic studies of these compounds on human breast cancer MCF-7 cell line revealed that all the compounds were low-cytotoxic in the concentration range of 2.5-250 μM.