RESUMO
Two new (-)-muricatacin mimics bearing a furano-furanone ring and an oxygen isostere in the side chain have been designed and synthesized and their in vitro antiproliferative activity was evaluated against several human tumour cell lines. Both analogues showed an increased activity against HL-60 cells with 17- and 185-fold higher potency than (-)-muricatacin. A straightforward synthesis of (-)-muricatacin is also disclosed.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Desenho de Fármacos , Furanos/síntese química , Furanos/farmacologia , Annonaceae/química , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Furanos/química , Células HL-60 , Células HeLa , Humanos , Estrutura Molecular , Plantas Medicinais/química , EstereoisomerismoRESUMO
A facile synthesis of 7-epi-(-)-goniofufurone as well as the first synthesis of (-)-crassalactone C was achieved starting from D-xylose. A comparison of their in vitro antitumour activities with those observed for the corresponding naturally occurring enantiomers was provided.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Lactonas/síntese química , Lactonas/farmacologia , Xilose/química , Annonaceae/química , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Células Jurkat , Lactonas/química , Estrutura Molecular , Plantas Medicinais/química , Estereoisomerismo , Células Tumorais CultivadasRESUMO
A new divergent approach to (+)-goniofufurone (1) and 7-epi-(+)-goniofufurone (2), as well as the first total synthesis of crassalactone C (3), has been achieved starting from D-xylose. In a preliminary bioassay, all three natural products 1, 2, and 3 showed remarkable in vitro antiproliferative activities against K562, Raji, and HeLa neoplastic cell lines.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Lactonas/síntese química , Xilose/química , Annonaceae/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Lactonas/química , Lactonas/farmacologia , Estrutura Molecular , Plantas Medicinais/química , Células Tumorais CultivadasRESUMO
A divergent approach to the 7-oxa (-)-muricatacin analogue 2, the corresponding (+)-enantiomer ent-2 and the furanolactone 3 is reported starting from D-xylose. The resulting lactones have shown a potent and selective in vitro cytotoxicity against certain human neoplastic cell lines.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Furanos/síntese química , Furanos/farmacologia , Lactonas/síntese química , Lactonas/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Furanos/química , Humanos , Técnicas In Vitro , Lactonas/química , Conformação Molecular , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Methyl 2,3-anhydro-4-O-methanesulfonyl-alpha-d-ribopyranoside (12) was prepared through a new six-step sequence starting from d-arabinose. Chemical behaviour of 12 was further studied under solvolytic conditions and in the presence of azide anion as a nucleophile. Factors governing the regiochemistry of epoxide ring opening are briefly discussed.
Assuntos
Arabinose/química , Compostos de Epóxi/química , Azidas/química , Configuração de Carboidratos , Cromatografia em Camada Fina , Glicosídeos/química , Espectroscopia de Ressonância Magnética , Modelos Químicos , Espectrofotometria Infravermelho , TemperaturaRESUMO
This paper describes a straightforward divergent synthesis of (+)-goniofufurone mimics (4, 5 and 6) starting from d-xylose. In a preliminary bioassay, analogues 4 and 5 exhibited a submicromolar antiproliferative activity towards HL-60 cells, while the corresponding parent compound 1 was completely inactive against this cell line. At the same time, these molecules showed approximately 10-fold stronger cytotoxicity in the same cell line when compared to the standard anticancer drug doxorubicin (DOX). Analogue 6 displayed 18- and 3-fold higher potency in Raji cell line when compared to control compounds 1 and DOX, respectively. A new divergent route for the preparation of (+)-goniofufurone (1) and (+)-crassalactone C (3) from d-xylose is also disclosed.