RESUMO
ZJ-101, a structurally simplified analog of marine natural product superstolide A, was previously designed and synthesized in our laboratory. In the present study four new analogs of ZJ-101 were designed and synthesized to investigate the structure-activity relationship of the acetamide moiety of the molecule. The biological evaluation showed that the amide moiety is important for the molecule's anticancer activity. Replacing the amide with other functional groups such as a sulfonamide group, a carbamate group, and a urea group resulted in the decrease in anticancer activity.
Assuntos
Amidas , Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Humanos , Amidas/química , Amidas/farmacologia , Amidas/síntese química , Linhagem Celular Tumoral , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Macrolídeos/química , Macrolídeos/farmacologia , Macrolídeos/síntese química , Relação Dose-Resposta a DrogaRESUMO
ZJ-101 is a structurally simplified analog of marine natural product superstolide A that was previously designed and synthesized in our laboratory. Biological investigation shows that ZJ-101 maintains the potent anticancer activity of the original natural product with an undefined mechanism of action. To facilitate chemical biology study, a biotinylated ZJ-101 was synthesized and biologically evaluated.
Assuntos
Produtos Biológicos , Macrolídeos , Macrolídeos/farmacologia , Tetra-Hidronaftalenos/farmacologia , Produtos Biológicos/farmacologia , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure-activity relationship study, a new analog ZJ-109 was designed and synthesized to probe the importance of the lactone moiety of the molecule by replacing the lactone in ZJ-101 with a lactam. The biological evaluation showed that ZJ-109 is about 8-12 times less active against cancer cells in vitro than ZJ-101, suggesting that the lactone moiety of the molecule is important for its anticancer activity.
Assuntos
Antineoplásicos/farmacologia , Macrolídeos/farmacologia , Tetra-Hidronaftalenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Relação Estrutura-AtividadeRESUMO
Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure-activity relationship study, two new analogs, ZJ-105 and ZJ-106, were designed and synthesized to probe the importance of the conjugated trienyl lactone moiety of the molecule by replacing the C2-C3 double bond in ZJ-101 with a single bond and switching the geometry of the C4-C5 double bond in ZJ-101 from Z to E, respectively. Biological evaluation showed that ZJ-105 completely loses antiproliferative activity whereas ZJ-106 is significantly less active against cancer cells in vitro than ZJ-101, suggesting that the conjugated trienyl lactone moiety of the molecule is critical for its anticancer activity.
Assuntos
Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Lactonas/farmacologia , Macrolídeos/farmacologia , Poríferos/química , Tetra-Hidronaftalenos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lactonas/química , Macrolídeos/química , Macrolídeos/isolamento & purificação , Estrutura Molecular , Relação Estrutura-Atividade , Tetra-Hidronaftalenos/química , Tetra-Hidronaftalenos/isolamento & purificaçãoRESUMO
Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure-activity relationship study, a new analog ZJ-102 was designed and synthesized to probe the importance of the cyclohexenyl group through its replacement to a phenyl group using a concise and convergent synthetic approach. The biological evaluation showed that this new analog ZJ-102 is significantly less active against cancer cells in vitro than ZJ-101, suggesting that the cyclohexenyl ring (along with its two stereogenic centers) present in ZJ-101 is important for its anticancer activity.