Assuntos
Proteínas/química , Bibliotecas de Moléculas Pequenas , Proteínas 14-3-3/química , Animais , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/química , Humanos , Ligação Proteica , Proteínas Proto-Oncogênicas c-bcl-2/química , Tubulina (Proteína)/químicaRESUMO
Modulators of microtubule dynamics have received increasing attention because of their potential to stop cancer growth. Although it belongs to the category of complex protein-protein interactions (PPIs), which are generally considered difficult to modulate through small molecules, the use of microtubule is considered a well-validated target. There are a number of bioactive natural products and related compounds that are currently in use as drugs or in clinical trials as next generation anti-cancer agents. The present review article is focused on two such bioactive natural products, epothilone and halichondrin B, and covers some of the key papers published after 2005 that outline various synthetic approaches to obtain next generation structural analogs as well as the synthesis of hybrid compounds.
Assuntos
Produtos Biológicos/farmacologia , Epotilonas/farmacologia , Éteres Cíclicos/farmacologia , Macrolídeos/farmacologia , Moduladores de Tubulina/farmacologia , Tubulina (Proteína)/metabolismo , Animais , Produtos Biológicos/síntese química , Produtos Biológicos/química , Epotilonas/síntese química , Epotilonas/química , Éteres Cíclicos/síntese química , Éteres Cíclicos/química , Humanos , Macrolídeos/síntese química , Macrolídeos/química , Estrutura Molecular , Relação Estrutura-Atividade , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/químicaRESUMO
A divergent approach to obtain a latrunculin family based hybrid macrocyclic toolbox is developed. A practical, stereoselective synthesis of a common substructure present in latrunculin A and latrunculol A was achieved. This was further utilized in the macrocyclic diversity synthesis. The amino acid moiety embedded in the 15-membered macrocyclic ring allows for the exploration of various chiral side chains as one of the diversity sites.
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Macrolídeos/síntese química , Tiazolidinas/síntese química , Aminoácidos/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Desenho de Fármacos , Macrolídeos/química , Modelos Moleculares , Estrutura Molecular , Tiazolidinas/químicaRESUMO
A practical and modular approach to obtain a diverse set of 14-membered macrocyclic compounds from carbohydrates is developed that utilizes functional groups at C-1 and C-5. The evaluation of this toolbox in various zebrafish assays led to the identification of 2.7f as an antiangiogenesis agent.