RESUMO
Inhibitors of varying potency have been developed for types I and II 3-dehydroquinate dehydratase (dehydroquinase), enzymes from the shikimate and quinate pathways that catalyse the dehydration of dehydroquinate to dehydroshikimate. These inhibitors have resulted from enzyme mechanistic studies and from the direct search for enzyme inhibitors with herbicidal, fungicidal or antimicrobial potential. This review discusses the design of the various inhibitors that have been produced so far and some structure-activity relationships. The majority of these inhibitors are based on dehydroquinate analogues, although some work has also been carried out on dehydroshikimate and bissulfonamides. Some discussion is also presented on advances in the synthesis of these types of compounds.
Assuntos
Inibidores Enzimáticos , Hidroliases/antagonistas & inibidores , Aspergillus nidulans/enzimologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Hidroliases/fisiologia , Estrutura Molecular , Mycobacterium tuberculosis/enzimologia , Salmonella typhimurium/enzimologia , Streptomyces coelicolor/enzimologia , Relação Estrutura-Atividade , Especificidade por SubstratoRESUMO
We describe new methodology for the synthesis of symmetric bis-benzimidazoles carrying 2-aryl moieties, including 2-[4-(3'-aminopropoxy)phenyl] and 2-[4-(3'-aminopropanamido)phenyl] substituents, together with the synthesis of novel hybrid molecules comprising bis-benzimidazoles in ester and amide combination with the N-mustard chlorambucil. The in vitro activities of these compounds against five cancer cell lines are also provided.
Assuntos
Benzimidazóis/química , Benzimidazóis/toxicidade , Divisão Celular/efeitos dos fármacos , Mecloretamina/química , Amidas , Pareamento de Bases , Sequência de Bases , Benzaldeídos/química , Linhagem Celular Tumoral , Clorambucila/farmacologia , Cristalografia por Raios X , DNA de Neoplasias/química , DNA de Neoplasias/efeitos dos fármacos , Ésteres , Humanos , Mecloretamina/toxicidade , Modelos Moleculares , Conformação Molecular , Oligodesoxirribonucleotídeos/química , Pirrolidinas/química , RodaminasRESUMO
A versatile approach for the enantioselective synthesis of functionalised beta-hydroxy N-acetylcysteamine thiol esters has been developed which allows the facile incorporation of isotopic labels. It has been shown that a remarkable reversal of selectivity occurs in the titanium mediated aldol reaction of acyloxazolidinone using either (S)- or (R)-tert-butyldimethylsilyloxybutanal. The aldol products are valuable intermediates in the synthesis of 4-hydroxy-6-substituted delta-lactones.