RESUMO
The synthesis of a set of digitoxigenin neogluco/xylosides and corresponding study of their anticancer SAR revealed sugar amine regiochemistry has a dramatic effect upon activity. Specifically, this study noted sugar 3-amino followed by 4-amino-substitution to be most advantageous where the solvent accessibility of the appended amine within neoglycoside-Na(+),K(+)-ATPase docked models correlated with increased anticancer potency. This study presents a preliminary model for potential further warhead optimization in the context of antibody-directed steroidal glycosides and extends the demonstrated compatibility of aminosugars in the context of neoglycosylation.
RESUMO
A facile route to perillyl alcohol (POH) differential glycosylation and the corresponding synthesis of a set of 34 POH glycosides is reported. Subsequent in vitro studies revealed a sugar dependent antiproliferative activity and the inhibition of S6 ribosomal protein phosphorylation as a putative mechanism of representative POH glycosides. The most active glycoside from this cumulative study (4'-azido-d-glucoside, PG9) represents one of the most cytotoxic POH analogues reported to date.
Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Glicosídeos/farmacologia , Monoterpenos/química , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/química , Western Blotting , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glicosídeos/síntese química , Glicosídeos/química , Humanos , Concentração Inibidora 50 , Modelos Químicos , Estrutura Molecular , Fosfoproteínas/metabolismo , Fosforilação/efeitos dos fármacosRESUMO
Although bacterial iterative type I polyketide synthases are now known to participate in the biosynthesis of a small set of diverse natural products, the subsequent downstream modification of the resulting polyketide products is poorly understood. We report the functional characterization of the putative orsellinic acid C2-O-methyltransferase, which is involved in calicheamicin biosynthesis. This study suggests that C2-O-methylation precedes C3-hydroxylation/methylation and C5-iodination and requires a coenzyme A- or acyl carrier protein-bound substrate.
Assuntos
Bactérias/enzimologia , Metiltransferases/metabolismo , Resorcinóis/metabolismo , Bactérias/química , Bactérias/metabolismo , Hidroxilação , Cinética , Metilação , Modelos Moleculares , Policetídeo Sintases/metabolismo , Estrutura Terciária de Proteína , S-Adenosilmetionina/metabolismo , Streptomyces/química , Streptomyces/enzimologia , Streptomyces/metabolismo , Especificidade por SubstratoRESUMO
N-Furoylated L-threonine-, serine-, or cysteine-based aminoacetals are coupled with o-aminoketones or aldehydes to offer rapid access to diverse enantiopure polyheterocycles possessing conformationally locked aminoglycoside-containing molecular scaffolds. The key step involves photogeneration of azaxylylenes which undergo [4 + 4] or [4 + 2] cycloadditions to the tethered furoyl pendants.
Assuntos
Aminas/química , Dicetopiperazinas/química , Processos Fotoquímicos , Estrutura Molecular , EstereoisomerismoRESUMO
A simple and convenient methodology for selective sulfonation of aromatic compounds using sulfuric acid under sonication is described. The present methodology shows a considerable enhancement in the reaction rate along with improved selectivity compared with the reactions performed under silent conditions. The effect of various parameters such as agitation speed, sulfuric acid concentration, and temperature on reaction system have been investigated and are explained on the basis of ultrasonically generated cavitational effects.
Assuntos
Hidrocarbonetos Aromáticos/química , Sonicação , Sulfonas/síntese química , Ácidos Sulfúricos/química , Estrutura Molecular , Estereoisomerismo , Sulfonas/químicaRESUMO
Naphthols were selectively coupled under sonication using Fe(+3) impregnated pillared Montmorillonite K10 and TBHP as an oxidant. Considerable enhancement in the reaction rate was observed under sonication as compared to the reaction performed under silent condition. The activity of catalyst was compared with other Fe clay catalysts. Various parameters like solvent, catalyst and TBHP concentration has been studied. The heterogeneous active catalyst K10-FePLS120 was recycled without loss in activity and selectivity performance.
Assuntos
Bentonita/química , Ferro/química , Naftalenos/química , Naftalenos/síntese química , Oxidantes/química , terc-Butil Hidroperóxido/química , Catálise , Química/métodos , Cromatografia Líquida de Alta Pressão/métodos , Modelos Químicos , Solventes/química , Fatores de Tempo , Difração de Raios XRESUMO
Phenols are selectively nitrated to o-nitrophenol along with rate enhancement using dilute nitric acid (6 wt%)/tetra butyl ammonium bromide (TBAB) under sonication. The selectivity can also be reversed to p-nitrophenol using NaBr as a catalyst. Kinetic analysis of nitration of phenol both with and without sonication has been investigated by variation of reaction parameters such as catalyst, nitric acid and substrate concentration.
