RESUMEN
Fifty 2-[(arylidene)amino]-4,5-cycloalkyl[b]thiophene-3-carbonitrile derivatives were screened for their in vitro antifungal activities against Candida krusei and Cryptococcus neoformans. Based on experimentally determined minimum inhibitory concentration (MIC) values, we conducted computer-aided drug design studies [molecular modelling, chemometric tools (CPCA, PCA, PLS) and QSAR-3D] that enable the prediction of three-dimensional structural characteristics that influence the antifungal activities of these derivatives. These predictions provide direction with regard to the syntheses of new derivatives with improved biological activities, which can be used as therapeutic alternatives for the treatment of fungal infections.
Asunto(s)
Antifúngicos/farmacología , Diseño Asistido por Computadora , Diseño de Fármacos , Nitrilos/farmacología , Tiofenos/farmacología , Candida/efectos de los fármacos , Simulación por Computador , Cryptococcus neoformans/efectos de los fármacos , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Análisis de Componente Principal , Relación Estructura-Actividad Cuantitativa , Análisis de Regresión , Propiedades de SuperficieRESUMEN
Here we report the development of MolPredictX, an innovate and freely accessible web interface for biological activity predictions of query molecules. MolPredictX utilizes in-house QSAR models to provide 27 qualitative predictions (active or inactive), and quantitative probabilities for bioactivity against parasitic (Trypanosoma and Leishmania), viral (Dengue, Sars-CoV and Hepatitis C), pathogenic yeast (Candida albicans), bacterial (Salmonella enterica and Escherichia coli), and Alzheimer disease enzymes. In this article, we introduce the methodology and usability of this webtool, highlighting its potential role in the development of new drugs against a variety of diseases. MolPredictX is undergoing continuous development and is freely available at https://www.molpredictx.ufpb.br/.
Asunto(s)
Aprendizaje AutomáticoRESUMEN
Chagas disease, a neglected tropical disease, is endemic in 21â Latin American countries and particularly prevalent in Brazil. Chagas disease has drawn more attention in recent years due to its expansion into non-endemic areas. The aim of this work was to computationally identify and experimentally validate the natural products from an Annonaceae family as antichagasic agents. Through the ligand-based virtual screening, we identified 57â molecules with potential activity against the epimastigote form of T.â cruzi. Then, 16â molecules were analyzed in the inâ vitro study, of which, six molecules displayed previously unknown antiepimastigote activity. We also evaluated these six molecules for trypanocidal activity. We observed that all six molecules have potential activity against the amastigote form, but no molecules were active against the trypomastigote form. 13-Epicupressic acid seems to be the most promising, as it was predicted as an active compound in the in silico study against the amastigote form of T.â cruzi, in addition to having inâ vitro activity against the epimastigote form.
Asunto(s)
Annonaceae , Productos Biológicos , Enfermedad de Chagas , Tripanocidas , Trypanosoma cruzi , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Enfermedad de Chagas/tratamiento farmacológico , Tripanocidas/farmacología , Tripanocidas/uso terapéuticoRESUMEN
Cancer is a life-threatening disease killing millions of people globally. Among various medical treatments, nano-medicines are gaining importance continuously. Many nanocarriers have been developed for treatment, but polymerically-based ones are acquiring importance due to their targeting capabilities, biodegradability, biocompatibility, capacity for drug loading and long blood circulation time. The present article describes progress in polymeric nano-medicines for theranostic cancer treatment, which includes cancer diagnosis and treatment in a single dosage form. The article covers the applications of natural and synthetic polymers in cancer diagnosis and treatment. Efforts were also made to discuss the merits and demerits of such polymers; the status of approved nano-medicines; and future perspectives.