Attar Salahuddin

Synthesis, characterization and biological evaluation of novel 6-ferrocenyl-4-aryl-2-substituted pyrimidine derivatives.

A new series of 6-ferrocenyl-4-aryl-2-substituted pyrimidines were synthesized and evaluated for in vitro antiamoebic activity against HM1:IMSS strain of Entamoeba histolytica. Out of 16 compounds 10 compounds have shown IC(50) values in the range of 0.41-1.73 microM and 1.80 microM. Pyrimidine derivatives having thiomethyl group, chloro group and mono-, di-, and trimethoxy substitution, exhibited higher antiamoebic activity than the reference drug metronidazole (IC(50)=1.80 microM). The toxicological studies of these compounds on human kidney epithelial cell line showed that all compounds were non-toxic. 4-(4-Chlorophenyl)-6-ferrocenyl-2-piperidin-1-yl-pyrimidine (4f) was found most active (IC(50)=0.41 microM) and least toxic among all the compounds.

Synthesis, characterization, antiamoebic activity and cytotoxicity of novel series of pyrazoline derivatives bearing quinoline tail

The cyclization of chalcones (1a-1j) with 2-(quinolin-8-yloxy) acetohydrazide (2) under basic condition led to the formation of new compounds, pyrazoline derivatives (3a-3j). In vitro antiamoebic activity was performed against HM1: IMSS strain of Entamoeba histolytica. The results showed that the compounds 3d, 3g, 3h, and 3j exhibited promising antiamoebic activity (IC(50) = 0.05 microM, 0.31 microM, 0.06 microM, 0.29 microM) respectively than the standard drug metronidazole (IC(50) = 1.84 microM). The toxicological studies of these compounds on human breast cancer MCF-7 cell line showed that all the compounds 3d, 3g, 3h, 3j and metronidazole were nontoxic at the concentration range of 1.56-50 microM.

Antiprotozoal activity of chloroquinoline based chalcones.

A new series of chloroquinoline based chalcones were synthesized and evaluated for in vitro antiamoebic and antimalarial activities. The results showed that out of fifteen compounds, four were found to be more active against the Entamoeba histolytica; while one compound was moderatively active compared to the standard drug metronidazole (IC50=1.46 μM). In contrast, in vitro antimalarial activity against the chloroquine-sensitive (3D7) strain of P. falciparum indicated relatively low activity when compared to controls such as chloroquine and quinine (IC50=0.0065 μM and 0.14 μM, respectively). The toxicological studies of these compounds on human breast cancer MCF-7 cell line showed that all the compounds were non-toxic at the concentration range of 1.56-50 μM.

Synthesis, characterization and antiamoebic activity of some hydrazone and azole derivatives bearing pyridyl moiety as a promising heterocyclic scaffold

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.

Metronidazole thiosalicylate conjugates: synthesis, crystal structure, docking studies and antiamoebic activity.

Metronidazole thiosalicylate conjugates were synthesized and crystallised in order to discover new molecules having better efficacy than therapeutically administered drug metronidazole, used against Entamoeba histolytica. The three compounds (4-6) showed lower IC(50) values than metronidazole on HM1:IMSS strain of E. histolytica and displayed low cytotoxicity on MCF-7 cell line. In order to get an insight into the mechanisms of action of these compounds, a homology model of E. histolytica thioredoxin reductase (EhTHRase) was constructed and molecular docking was performed into the binding pocket to identify the nature of interactions. The docking studies suggest that the improved inhibitory activity of the newly synthesised metronidazole analogues could be due to involvement of the additional hydrophobic interactions in the binding mode. The result of the present study indicates the molecular fragments that play an essential role in improving the antiamoebic activity.

Thiosemicarbazone fragment embedded within 1,2,4-triazole ring as inhibitors of Entamoeba histolytica.

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.

Synthesis, characterization, antiamoebic activity and cytotoxicity of new pyrazolo[3, 4-d]pyrimidine-6-one derivatives

A new series of pyrazolo[3,4-d]pyrimidine-6-one derivatives (2a–2j) were prepared by using the Biginelli multicomponent cyclocondensation of 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (1a), different aromatic aldehydes, and urea with a catalytic amount of HCl at reflux temperature. These compounds were characterized by IR, 1H NMR, 13C NMR, and Mass spectral data. In vitro antiamoebic activity was performed against HM1:IMSS strain of Entamoeba histolytica. The results showed that the compounds 2b, 2i, and 2j with IC50 values of 0.37 µM, 0.04 µM, and 0.06 µM, respectively, exhibited better antiamoebic activity than the standard drug metronidazole (IC50 = 1.33 µM). The toxicological studies of these compounds on human breast cancer MCF-7 cell line showed that the compounds 2b, 2i, and 2j exhibited >80% viability at the concentration range of 1.56–50 µM.