ABSTRACT
Although the parasitic infection Chagas' disease was described over 100 years ago, even now there are not suitable drugs. The available drugs nifurtimox and benznidazole have limited efficacies and tolerances, with proven mutagenic effects. Attempting to find appropriate drugs to deal with this problem, here we report on the development and pharmacological characterization of new amide-containing thiazoles. In the present study, we evaluated the in vitro and in vivo effects of new candidates against Trypanosoma cruzi, the etiological agent of Chagas' disease. The lead amide-containing thiazole derivative had potent in vitro activity, an absence of both in vitro mutagenic and in vivo clastogenic effects, and excellent in vitro selectivity and in vivo tolerance. The compound suppressed parasitemia in mice, modifying the anti-T. cruzi antibodies like the reference drug, benznidazole, and displayed the lowest mortality among the tested drugs. The present evidence suggests that this compound is a promising anti-T. cruzi agent surpassing the lead optimization stage in drug development and leading to a candidate for preclinical study.
Subject(s)
Amides/pharmacology , Chagas Disease/drug therapy , Thiazoles/pharmacology , Trypanocidal Agents/pharmacology , Amides/chemical synthesis , Animals , Chagas Disease/pathology , Drug Discovery , Male , Mice , Mice, Inbred BALB C , Thiazoles/chemical synthesis , Trypanosoma cruzi/drug effects , Trypanosoma cruzi/growth & developmentABSTRACT
La leucemia mieloide aguda es una neoplasia hematopoyética caracterizada por la proliferación clonal de blastos inmaduros en médulas ósea interfiriendo con sus funciones normales. Tiene una supervivencia aproximada de 35% afectando principalmente a adultos mayores de 60 años y niños menores de un año y preferentemente al sexo masculino. Un hallazgo frecuente es la presencia de la translocación cromosómica t (8; 21) (q22; q22) que involucra a los genes RUNX1 y RUNX1T1. La detección de esta alteración tiene implicancia diagnóstica y pronóstica de la enfermedad. El objetivo de este trabajo es describir y reportar dos casos de leucemia mieloide aguda en pacientes masculinos de 14 y 24 años que presentaron clínica, laboratorio y morfología típicos de la enfermedad pero con edad de aparición no habitual, enfatizando además, el pronóstico bueno desde el punto de vista citogenético de esta translocación en ambos casos.
Acute myeloid leukemia is a haematopoietic neoplasia characterized by clonal proliferation of immature blasts in bone marrow, interfering with its normal functions. Overall survival is about 35% affecting mainly male adults over 60 years old and infants under one year old. Genetic translocation t(8;21)(q22;q22) is a recurrent finding and involves RUNX1 and RUNX1T1 genes. The detection of this genetic translocation is relevant to the diagnosis and prognosis of the disease. The objective of this work is to report two cases of acute myeloid leukaemia in 14 and 24 years old male patients with typical clinical, laboratorial and morphological findings but with unusual appearing ages, emphasizing the good prognosis from the genetic point of view of this translocation in both cases.
