ABSTRACT
Salicylaldehyde 2-chlorobenzoyl hydrazone (H(2)LASSBio-466), salicylaldehyde 4-chlorobenzoyl hydrazone (H(2)LASSBio-1064) and their complexes [Zn(LASSBio-466)H(2)O](2) (1) and [Zn(HLASSBio-1064)Cl](2) (2) were evaluated in animal models of peripheral and central nociception, and acute inflammation. All studied compounds significantly inhibited acetic acid-induced writhing response. Upon coordination the anti-nociceptive activity was favored in the complex 1. H(2)LASSBio-466 inhibited only the first phase of the formalin test, while 1 was active in the second phase, like indomethacin, indicating its ability to inhibit nociception associated with the inflammatory response. Hence coordination to zinc(II) altered the pharmacological profile of H(2)LASSBio-466. H(2)LASSBio-1064 inhibited both phases but this effect was not improved by coordination. The studied compounds did not increase the latency of response in the hot plate model, indicating their lack of central anti-nociceptive activity. All compounds showed levels of inhibition of zymosan-induced peritonitis comparable or superior to indomethacin, indicating an expressive anti-inflammatory profile.
Subject(s)
Aldehydes/chemistry , Analgesics/pharmacology , Anti-Inflammatory Agents/pharmacology , Coordination Complexes/pharmacology , Hydrazones/chemistry , Inflammation/drug therapy , Pain , Peritonitis/drug therapy , Acetic Acid/adverse effects , Analgesics/chemical synthesis , Animals , Anti-Inflammatory Agents/chemical synthesis , Coordination Complexes/chemical synthesis , Crystallography, X-Ray , Dipyrone/pharmacology , Female , Formaldehyde/adverse effects , Hot Temperature/adverse effects , Indomethacin/pharmacology , Inflammation/chemically induced , Inflammation/physiopathology , Magnetic Resonance Spectroscopy , Male , Mice , Morphine/pharmacology , Pain/chemically induced , Pain/drug therapy , Pain/physiopathology , Pain/prevention & control , Pain Measurement , Peritonitis/chemically induced , Peritonitis/physiopathology , Zinc/metabolism , Zymosan/adverse effectsABSTRACT
N(4)-methyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4M, 1), N(4),N(4)-dimethyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4DM, 2) and N(4)-piperidyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4Pip, 3) and their copper(II) complexes [Cu(4NO(2)Ac4M)(2)] (4), [Cu(4NO(2)Ac4DM)(2)] (5) and [Cu(4NO(2)Ac4Pip)(2)] (6) were tested for their in vitro ability to inhibit the growth of Trypanosoma cruzi epimastigote forms. H4NO(2)Ac4DM (2), [Cu(4NO(2)Ac4M)(2)] (4) and [Cu(4NO(2)Ac4DM)(2)] (5) proved to be as active as the clinical reference drugs nifurtimox and benznidazol. Taking into consideration the serious side effects and the poor efficacy of the reference drugs, as well as the appearance of resistance during treatment, the studied compounds could constitute a new class of anti-trypanosomal drug candidates.
Subject(s)
Acetophenones/chemical synthesis , Chelating Agents/chemical synthesis , Copper , Thiosemicarbazones/chemical synthesis , Trypanocidal Agents/chemical synthesis , Acetophenones/chemistry , Acetophenones/pharmacology , Animals , Chelating Agents/chemistry , Crystallography, X-Ray , Electrochemistry , Electron Spin Resonance Spectroscopy , Humans , In Vitro Techniques , Macrophages/drug effects , Macrophages/parasitology , Magnetic Resonance Spectroscopy , Molecular Structure , Thiosemicarbazones/chemistry , Thiosemicarbazones/pharmacology , Trypanocidal Agents/chemistry , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effectsABSTRACT
The title compound, C(13)H(12)N(4)O, crystallizes with two independent mol-ecules in the asymmetric unit. The compound crystallizes as the ZE isomer, where Z and E refer to the configuration around the C=N and N-C bonds, respectively, with an N-Hâ¯N(py) (py is pyridine) intra-molecular hydrogen bond. The dihedral angles between the least-squares planes through the semicarbazone group and the pyridyl ring are 22.70â (9) and 27.26â (9)° for the two mol-ecules. There are intermolecular N-Hâ¯O hydrogen bonds.
ABSTRACT
Structural studies and an investigation of the cytotoxic activity of Sn(IV) complexes with N(4)-phenyl-2-benzoylpyridine thiosemicarbazone (H2Bz4Ph) were carried out. The crystal and molecular structures of [Sn(2Bz4Ph)Cl3].CH3CH2OH (1) and [Sn(2Bz4Ph)BuCl2].H2O (Bu = butyl group) (2) were determined. Both compounds present octahedral coordination geometry with the 2Bz4Ph anionic ligand behaving as tridentate on the metal ion. A comparative study of the structures of these compounds along with that of [Sn(2Bz4Ph)Bu2Cl] (3) determined before is presented. The cytotoxicity of H2Bz4Ph and its Sn(IV) complexes was investigated against the MCF-7, TK-10 and UACC-62 human tumor cell lines. Among the three complexes, 3 proved to be better as cytotoxic agent than the clinically used drug etoposide. H2Bz4Ph and all complexes were able to induce apoptosis in UACC-62 cells.
