ABSTRACT
New imidazole derived thiosemicarbazones and hydrazones were prepared by condensation of 4(5)-imidazole carboxaldehyde, 4-(1H-imidazole-1-yl)benzaldehyde and 4-(1H-imidazole-1-yl)acetophenone with a thiosemicarbazide or hydrazide. All compounds were characterized by quantitative elemental analysis, IR and NMR techniques. Eight structures were determined by single crystal X-ray diffraction. The antifungal activities of the compounds were evaluated. None of the compounds exhibited significant activity against Aspergillus flavus and Candida albicans, while 4(5)-imidazolecarboxaldehyde thiosemicarbazone (ImT) and 4-(1H-imidazole-1-yl)benzaldehyde thiosemicabazone (4ImBzT) were highly and selectively active against Cladosporium cladosporioides. 4(5)-Imidazolecarboxaldehyde benzoyl hydrazone (4(5)ImPh), 4(5)-imidazolecarboxaldehyde-para-chlorobenzoyl hydrazone (4(5)ImpClPh), 4(5)-imidazolecarboxaldehyde-para-nitrobenzoyl hydrazone (4(5)ImpNO2Ph), 4-(imidazole-1-yl)acetophenone-para-chloro-benzoyl hydrazone (4ImAcpClPh) and 4-(imidazole-1-yl)acetophenone-para-nitro-benzoylhydrazone (4ImAcpNO2Ph) were highly active against Candida glabrata. 4(5)ImpClPh and 4(5)ImpNO2Ph were very effective against C. cladosporioides. In many cases, activity was superior to that of the reference compound nystatin.
Subject(s)
Antifungal Agents/pharmacology , Hydrazones/pharmacology , Imidazoles/chemistry , Thiosemicarbazones/pharmacology , Antifungal Agents/chemistry , Aspergillus flavus/drug effects , Candida albicans/drug effects , Cladosporium/drug effects , Crops, Agricultural , Hydrazones/chemistry , Hydrogen Bonding , Microbial Sensitivity Tests , Models, Molecular , Molecular Conformation , Nystatin/pharmacology , Plant Diseases/microbiology , Thiosemicarbazones/chemistry , X-Ray DiffractionABSTRACT
Complexes [Bi(2Fo4Ph)Cl(2)] (1), [Bi(2Ac4Ph)Cl(2)] (2), [Bi(2Bz4Ph)Cl(2)] (3), [Bi(H(2)Gy3DH)Cl(3)] (4), [Bi(H(2)Gy4Et)(OH)(2)Cl] (5), and [Bi(H(2)Gy4Ph)Cl(3)] (6) were prepared with pyridine-2-carbaldehyde 4-phenylthiosemicarbazone (H2Fo4Ph), 1-(pyridin-2-yl)ethanone 4-phenylthiosemicarbazone (H2Ac4Ph), phenyl(pyridin-2-yl)methanone 4-phenylthiosemicarbazone (H2Bz4Ph), as well as with glyoxaldehyde bis(thiosemicarbazone) (H(2)Gy4DH) and its 4-Et (H(2)Gy4Et) and 4-Ph (H(2)Gy4Ph) derivatives. The complexes exhibited antibacterial activities against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, and Pseudomonas aeruginosa. Coordination to Bi(III) proved to be an effective strategy to increase the antibacterial activity of the thiosemicarbazones and bis(thiosemicarbazones).
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Bismuth/chemistry , Coordination Complexes/chemical synthesis , Thiosemicarbazones/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Crystallography, X-Ray , Enterococcus/drug effects , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Models, Molecular , Molecular Structure , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Thiosemicarbazones/chemistry , Thiosemicarbazones/pharmacologyABSTRACT
Complexes [Sb(QN)(2)Cl] (1), [Sb(QC)(2)Cl] (2) and [Sb(QI)(2)Cl] (3) were obtained with 8-hydroxyquinoline (HQN), 5-chloro-8-hydroxyquinoline (HQC) and 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol, HQI). The quinoline derivatives and their antimony(III) complexes were evaluated for their anti-trypanosomal activity as well as for their cytotoxicity against HL-60 and Jurkat human leukemia cell lines. Upon coordination to antimony(III) the anti-trypanosomal activity of HQC and HQI increases, the highest improvement being observed for complex (3), which was the most active among all studied compounds against both epimastigote and trypomastigote forms of Trypanosoma cruzi. All quinoline derivatives proved to be cytotoxic against both leukemia cell lineages. Upon coordination to antimony(III) the cytotoxicity of HQN improved against Jurkat leukemia cells. While SbCl(3) proved to be cytotoxic against HL-60 cells, it was not active against Jurkat cells. However, its coordination to the quinoline derivatives resulted in complexes with significant cytotoxicity against Jurkat cells.
Subject(s)
Antimony/chemistry , Antineoplastic Agents/pharmacology , Antiprotozoal Agents/pharmacology , Hydroxyquinolines/chemistry , Organometallic Compounds/pharmacology , Trypanosoma cruzi/drug effects , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , Male , Mice , Mice, Inbred BALB C , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry , Parasitic Sensitivity Tests , Spleen/cytology , Spleen/drug effects , Structure-Activity Relationship , Trypanosoma cruzi/growth & developmentABSTRACT
The antimony(III) complexes [Sb(2Bz4DH)Cl(2)] (1), [Sb(H2Bz4M)Cl(3)] x 2 H(2)O (2) and [Sb(2Bz4Ph)Cl(2)] (3) were obtained with 2-benzoylpyridine thiosemicarbazone (H2Bz4DH) and its N(4)-methyl (H2Bz4M) and N(4)-phenyl (H2Bz4Ph) derivatives. H2Bz4DH, H2Bz4Ph and complexes (1-3) exhibited high cytotoxic activity against HL-60 and Jurkat human leukemia cell lines. When these compounds were tested against HL-60 cells with ectopic expression of BcrAbl, Bcl-2 or Bcl-X(L), which confer resistance to apoptosis against a variety of death-inducing agents, the cytotoxicity was much lower, indicating apoptosis to be part of their mechanism of action. The cytotoxic activity of complexes 2 and 3 against HL-60 and Jurkat cells was significantly higher than that of the corresponding thiosemicarbazones, suggesting coordination to be an interesting strategy of cytotoxic dose reduction.
