RESUMEN
A neural model based on a numerical molecular representation using CODES program to predict oral absorption of any structure is described. This model predicts both high and low-absorbed compounds with a global accuracy level of 74%. CODES/ANN methodology shows promising utilities not only as a conventional in silico tool in high-throughput screening or improvement of absorption capabilities procedures but also the improvement of in vitro-in vivo correlation could be addressed.
Asunto(s)
Modelos Químicos , Tecnología Farmacéutica , Administración Oral , Humanos , Redes Neurales de la Computación , Permeabilidad , Relación Estructura-Actividad CuantitativaRESUMEN
Chagas disease, also known as American trypanosomiasis, is caused by infection with the protozoan parasite Trypanosoma cruzi. The Pan American Health Organization (PAHO) estimates that currently 7.7 million of people have Trypanosoma cruzi infection in the 21 endemic countries from the southern and southwestern United States to central Argentina and Chile. The only approved therapeutics for the treatment of Chagas disease are two nitroheterocyclic compounds as a nitrofuran (nifurtimox; Lampit) and a nitroimidazole (benznidazole; Rochagan). However, the anti-Trypanosoma cruzi activities of these compounds were discovered empirically over three decades ago. The treatment of Chagas disease with nifurtimox or benznidazole is unsatisfactory because of their limited efficacy in the prevalent chronic stage of the disease and their toxic side effects. In this context, this article will review the current knowledge of the different aspects involved in this illness, such as Trypanosoma cruzi transmission, physiology and biochemistry of the etiological agent, epidemiological aspects and current treatments for American trypanosomiasis. An important section of this review will focus on the different strategies in drug discovery for Chagas disease, including methodology, in vitro screening studies against whole parasites, novel rationally developed approaches on the basis of the increasing knowledge of the biochemistry of Trypanosoma cruzi and the recent progress in the understanding and validation of several targets for the therapy of Chagas's disease. A summary of the most relevant drug targets such as sterol biosynthesis pathway, cysteine protease pathway, pyrophosphate metabolism and purine salvage pathway will be reviewed. Moreover, recent studies regarding other strategies currently under development including thiol-dependent redox metabolism, lysophospholipid analogues and DNA binders will also be discussed.
Asunto(s)
Enfermedad de Chagas/etiología , Trypanosoma cruzi/efectos de los fármacos , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/epidemiología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/uso terapéutico , Ergosterol/biosíntesis , Ergosterol/metabolismo , Glutatión/análogos & derivados , Glutatión/química , Glutatión/uso terapéutico , Humanos , Hipoxantina Fosforribosiltransferasa/metabolismo , Espermidina/análogos & derivados , Espermidina/química , Espermidina/uso terapéuticoRESUMEN
Alzheimer's disease is a chronic and progressive neurodegenerative disorder. The presence of functional cannabinoid CB2 receptors in central nervous system (CNS) has provoked that this receptor and its agonist ligands are now considered as promising pharmacological targets for neurological diseases. Herein, we review the evidences supporting the potential role of the ECS as a therapeutic target, focused on CB2 receptor and its ligands, for the treatment of Alzheimer's disease.