ABSTRACT
Chagas' disease constitutes a therapeutic challenge because presently available drugs have wide toxicity to the host and are generally ineffective in the chronic stages of the disease. A series of oxazolo(thiazolo)pyridene derivatives were studied on Trypanosoma cruzi epimastigote growth and oxygen consumption and their electrochemical (redox) potentials and lipophilicity. The derivatives produced different degrees of parasite growth and respiration inhibition on CL Brener, LQ, and Tulahuen strains of T. cruzi epimastigotes. Respiratory chain inhibition appears to be a determinant of the trypanosomicidal activity of these compounds, since a significant correlation between respiration and culture growth inhibition was found. A similar correlation was found, within the different structural subfamilies, between toxic effects and the ability of the compounds to be oxidized in aqueous media. The inhibition of respiration and of parasite growth in culture increases with the lipophilicity of the substituents on the oxazolopyridine nucleus. No difference in the action of these derivatives was found among the different parasite strains. It is concluded that these compounds may have a potential usefulness in the treatment of Chagas' disease.
Subject(s)
Oxygen Consumption/drug effects , Pyridines/pharmacology , Trypanosoma cruzi/drug effects , Animals , Lipid Metabolism , Oxazoles/chemistry , Oxidation-Reduction , Pyridines/chemistry , Structure-Activity Relationship , Thiazoles/chemistry , Trypanosoma cruzi/growth & development , Trypanosoma cruzi/metabolismABSTRACT
Several prenylhydroquinones have been prepared through Diels-Alder condensation, further functionalized or degraded chemically and then evaluated for their cytotoxic activity against some neoplastic cultured cell lines. A number of them have shown IC50 values under the microM level.
Subject(s)
Antineoplastic Agents/chemical synthesis , Hydroquinones/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Screening Assays, Antitumor , Humans , Hydroquinones/chemistry , Hydroquinones/pharmacology , Magnetic Resonance Spectroscopy , Molecular Structure , Spectroscopy, Fourier Transform Infrared , Tumor Cells, CulturedABSTRACT
A series of 3-chloro-phenyl-1,4-dihydropyridine derivatives produced different degrees of inhibition of parasite growth and respiration on clone Brener, LQ and Tulahuen strains of Trypanosome cruzi epimastigotes. Respiratory chain inhibition appears to be a posible determinant of the trypanosomicidal activity of this compounds. No difference in the action of these derivatives was found among the different parasite strains. For comparative purposes, the inhibitory effects of felodipine and nicardipine are also reported. A good correlation between toxic effects and the easiness of oxidation of the dihydripyridine ring was found. The presence of a fused ring on the dihydropyridine moiety significantly diminished the inhibitory effects.