Síntese de complexos de estanho e estudo da atividade antiparasitária e antimicrobiana de compostos nitroaromáticos derivados de bases de schiff

Abstract

This work describes the synthesis and characterization of new ligands and some corresponding organotin complexes. Two new carboxylic acids (1a) and (1b) and their corresponding sodium salts (2a) and (2b); two semicarbazones (SCa) and (SCb) derived of 6-nitropiperonal (a) and 5-(2-nitrophenyl)furfural (b); four novel thiosemicarbazones derivative of 5-(2-nitrophenyl)furfural with different groups NH(12)-R: methyl (TSMe), ethyl (TSEt), phenyl (TSPh) and hydrogen (TSH). These compounds were characterized by techniques such as: melting point, carbon, hydrogen and nitrogen analyses, infrared and multinuclear magnetic resonance spectroscopy; the compounds (1a), (1b), (SCb), (TSEt) e (TSPh) have the structure authenticated by X-ray crystallography. The new organotin (3a), (4a), (3b), (4b), (5a), (6a), (5b), (6b), (7a) and (7b) were characterized by melting point, elemental analysis, infrared, multinuclear magnetic resonance (1H, 13C and 119Sn) and 119Sn Mössbauer spectroscopies. The in vitro leishmanicidal activity of a series of carboxylic acids (1a) and (1b) and semicarbazones (SCa) and (SCb) were evaluated against Leishmania infantum. The biological activity of the compounds was represented in terms of the IC50. All compounds were active against L. infantum and the best activity was displayed by compound SCa. Comparisons of the redox potential of the compounds and leishmanicidal activity indicate that the presence of the electroactive nitro group is important for the biological activity. The inhibiting activity of compound (SCa) was comparable to that of the reference drug, SbCl3. Considering the important side effects and the low efficiency of SbCl3 in the case of resistance, compound (SCa) deserves further attention as a promising leishmanicidal drug for veterinary use. The in vitro antimicrobial activity of all ligands and organotin complexes has been evaluated against various type of microbes (Filamentous fungi): Aspergillus niger, Aspergillus flavus, Aspergillus parasiticus and Penicillium citrinum; (Yeast): Candida dubliniensis, Candida lusitaniae, Candida albicans, Candida tropicalis, Candida parapsilosis and Candida glabrata; (Gram positive bactéria): Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, Streptococcus sanguinis and (Gram negative bacteria): Escherichia coli, Citrobacter frendii, Salmonella typhimurium e Pseudomonas aeruginosa. The biological activity of the compounds was displayed in terms of the IC50. The complexes with butyl groups were more active than methyl ones among most of the studied species. XTT tests were performed in order to evaluate the cell viability after exposure of the microorganisms to complex (4b). It was observed that XTT was still transformed into formazan, for colonies of A. parasiticus, C. dubliniensis, C. albicans, L. monocytogenes and C. frendii, cultivated in the presence of complex (4b) in doses corresponding to the minimum inhibitory concentrations. The complex (4b) displayed a fungicide activity, in the presence of A. parasiticus, in concentrations varying from 400 to 6,25 ìmol L-1, or towards C. albicans in the range of concentration of 400 to 100 ìmol L-1. The other concentrations showed fungistatic activity, as well as for C. dubliniensis. The bactericidal activity was observed for C. frendii in the concentration of 400 ìmol L-1and others concentrations showed bacteriostatic activity, as well as for L. monocytogenes. Finally, the toxic effects of the carboxylic acids, their sodium salts and of complexes (1a)-(6a) and (1b)-(6b) were performed using Chlorella vulgaris. It was observed that the presence of butyl groups has enhanced the lipophilicity of complexes (4b) and (6b), increasing their ability to cross the microbe cell membrane.