Estudos de ligantes derivados de nitrobenzaldeído, nitroacetofenona, 1,2,4-triazina e memantina para a coordenação de metais de importância farmacológica

Abstract

Complexes [Bi(L)2Cl] (1,4) and [Bi(HL)2Cl3] (2,3) with meta-nitrobenzaldehydethiosemicarbazone (HL1), para-nitrobenzaldehydethiosemicarbazone (HL2), meta-nitroacetophenonethiosemicarbazone (HL3) and para-nitroacetophenone-thiosemicarbazone (HL4) were obtained and characterized by means of microanalyses and their infrared and ¹H, ¹³C, Dept, COSY and HMQC NMR spectra. Electrochemistry studies on the reduction of the nitro pharmacophoric group were performed. The compounds proved to be inactive against HT-29 colorectal cancer cells and against HEK-293 non-malignant cells in normoxia as well as in hypoxia conditions. They were also inactive against aerobic Gram positive and Gram negative bacteria, and against fungi. However, since their nitro reduction potentials are comparable to those of bio-reducible prodrugs, they should be tested against anaerobic bacterial strains and against trypanosoma, taking into consideration that similar nitro thiosemicarbazones and their metal complexes exhibited significant antitrypanosomal activity. (3,5-dimethyl-1-iminoadamantin)methyl)phenol (HL5) and N-(2-pyridinylmethilene)-3,5-dimethyl-1-amino-adamantin (L6) were synthesized in order to functionalize memantine with a chelating group. The compounds were characterized by means of microanalyses and their infrared and NMR spectra. The crystal structure of L6 was determined. The electronic spectra of HL5 and L6 were recorded as a function of time in DMSO and DMSO-buffer pH 7.2 and pH 1.2. HL5 proved to be stable in DMSO but hydrolyzed in aqueous media in both pH values. L6 revealed to be stable in DMSO and in DMSO-buffer at pH 7.2 and pH 1.2, indicating that this compound might be an interesting chelating agent to coordinate metals involved in neurodegenerative diseases. 3,3'-bis(propylsulfanyl)-5,5'-bi-1,2,4-triazine (L7) was synthesized as a ligand to coordinate Pd(II) and Pt(II), aiming to obtain novel antineoplastic drug candidates. [Pd(L7)Cl2] (5) and [Pt(L7)2]Cl2∙2KCl (6) were obtained and characterized by means of microanalyses and their infrared and ¹H, ¹³C and 195Pt (6) NMR spectra. Electronic spectra showed that 5 and 6 react with DMSO, with possible replacement of the ligands by the solvent followed by decomplexation. The electronic spectra of 6 do not change in DMF but precipitation occurs in DMF-buffer precluding the evaluation of its bioactivities.