RESUMO
Chemotherapies, HIV infections, and treatments to block organ transplant rejection are creating a population of immunocompromised individuals at serious risk of systemic fungal infections. Since single-agent therapies are susceptible to failure due to either inherent or acquired resistance, alternative therapeutic approaches such as multi-agent therapies are needed. We have developed a bioinformatics-driven approach that efficiently predicts compound synergy for such combinatorial therapies. The approach uses chemogenomic profiles in order to identify compound profiles that have a statistically significant degree of similarity to a fluconazole profile. The compounds identified were then experimentally verified to be synergistic with fluconazole and with each other, in both Saccharomyces cerevisiae and the fungal pathogen Candida albicans. Our method is therefore capable of accurately predicting compound synergy to aid the development of combinatorial antifungal therapies.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Biologia Computacional , Desenho Assistido por Computador , Desenho de Fármacos , Fluconazol/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Animais , Antifúngicos/química , Antifúngicos/uso terapêutico , Candida albicans/genética , Candida albicans/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Farmacorresistência Fúngica/genética , Sinergismo Farmacológico , Quimioterapia Combinada , Fluconazol/química , Fluconazol/uso terapêutico , Regulação Fúngica da Expressão Gênica , Humanos , Modelos Moleculares , Estrutura Molecular , Reprodutibilidade dos Testes , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Relação Estrutura-AtividadeRESUMO
Complete asymmetric amplification of ethylenediammonium sulfate was achieved under continuous dissolution/crystallization conditions using an abrasion/grinding method.
Assuntos
Etilenodiaminas/química , Compostos de Amônio Quaternário/síntese química , Ácidos Sulfúricos/química , Fenômenos Químicos , Físico-Química , Cristalização , Ligação de Hidrogênio , Modelos Moleculares , Pressão , Compostos de Amônio Quaternário/química , Solubilidade , Estresse Mecânico , Fatores de TempoRESUMO
Spontaneous asymmetric generation of supramolecular chiral fibers was observed in the folding induced self-assembly of a lock-washer shaped foldamer. A secondary nucleation growth mechanism is proposed to explain the observed chiral amplification or deracemization of these supramolecular fibers.