RESUMO
The antiproliferative activity of a set of seven natural Amaryllidaceae alkaloids and 32 derivatives against four cancer cell lines (A2780, SW1573, T47-D and WiDr) was determined. The best antiproliferative activities were achieved with alkaloids derived from pancracine (2), haemanthamine (6) and haemantidine (7). For each skeleton, some structure-activity relationships were outlined.
Assuntos
Alcaloides/química , Alcaloides/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Alcaloides/síntese química , Antineoplásicos Fitogênicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Liliaceae/química , Relação Estrutura-AtividadeRESUMO
A set of twenty one lycorenine derivatives has been prepared from the alkaloid hippeastrine (1). The modifications performed on hippeastrine included some functional group transformations, structural simplification and preparation of dimers. All alkaloids were tested as potential antimalarial agents, being the hippeastrine dimers the most active compounds.
Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Antimaláricos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Alcaloides de Amaryllidaceae/síntese química , Alcaloides de Amaryllidaceae/química , Antimaláricos/síntese química , Antimaláricos/química , Dimerização , Humanos , Concentração Inibidora 50 , Modelos Químicos , Estrutura Molecular , Parasitemia/parasitologia , Parasitemia/prevenção & controle , Testes de Sensibilidade Parasitária , Relação Estrutura-AtividadeRESUMO
Thirty one derivatives were prepared from the natural alkaloids haemanthamine (1), haemanthidine (2) and 11-hydroxyvittatine (3). They were evaluated for their in vitro antimalarial activity against chloroquine-sensitive strains of Plasmodium falciparum and some structure-activity relationships were outlined. For haemanthamine derivatives having a methoxy group at C-3, the presence of a free hydroxyl group at C-11 is important for the activity. The double bond at C-1-C-2 plays also an important role to achieve good inhibitory activity. Compound 35 with two nicotinate groups at C-3 and at C-11 was the most active compound with a IC(50) = 0.8 ± 0.06 µM.
Assuntos
Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/farmacologia , Antimaláricos/síntese química , Antimaláricos/farmacologia , Fenantridinas/química , Fenantridinas/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Alcaloides de Amaryllidaceae/síntese química , Antimaláricos/química , Relação Dose-Resposta a Droga , Conformação Molecular , Testes de Sensibilidade Parasitária , Fenantridinas/síntese química , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Twenty seven lycorine derivatives were prepared and evaluated for their in vitro antimalarial activity against chloroquine-sensitive strains of Plasmodium falciparum. The best antiplasmodial activities were achieved with lycorine derivatives that present free hydroxyl groups at C-1 and C-2 or esterified as acetates or isobutyrates. The double bond C-2-C-3 is also important for the activity. Concerning to the antiplasmodial activity of the secolycorines, the higher values were obtained with the replacement of the methylenedioxy moiety by hydroxyl or acetate groups and with methyl substituent attached to the nitrogen atom.
Assuntos
Alcaloides de Amaryllidaceae/química , Antimaláricos/síntese química , Fenantridinas/química , Alcaloides de Amaryllidaceae/síntese química , Alcaloides de Amaryllidaceae/farmacologia , Antimaláricos/química , Antimaláricos/farmacologia , Fenantridinas/síntese química , Fenantridinas/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Relação Estrutura-AtividadeAssuntos
Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/classificação , Liliaceae/química , Extratos Vegetais/química , Alcaloides de Amaryllidaceae/síntese química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antiprotozoários/síntese química , Antiprotozoários/química , Antiprotozoários/farmacologia , Proliferação de Células/efeitos dos fármacos , Chlorocebus aethiops , Células HeLa , Humanos , Estrutura Molecular , Células VeroRESUMO
An unexpected rearrangement of haemanthamine-type alkaloids in the presence of halogenating agents has been found. Rearranged compounds present the 5,11-methanomorphantridine framework characteristic of montanine-type alkaloids. These compounds are difficult to obtain because of their scarcity in natural sources and because the synthetic approaches developed so far require numerous steps. Vibrational circular dichroism (VCD) spectroscopy was used to determine the absolute configuration of one of the rearranged compounds. Several rearranged alkaloids showed antimalarial activity.
Assuntos
Alcaloides/química , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/síntese química , Antimaláricos/química , Antimaláricos/síntese química , Isoquinolinas/química , Fenantridinas/química , Fenantridinas/síntese química , Alcaloides de Amaryllidaceae/farmacologia , Animais , Antimaláricos/farmacologia , Dicroísmo Circular , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Isomerismo , Modelos Moleculares , Estrutura Molecular , Fenantridinas/farmacologia , Plasmodium falciparum/efeitos dos fármacosRESUMO
Four new alkaloids (1-4) have been isolated from a methanolic extract of bulbs of Pancratium canariense, together with 12 known alkaloids (5-16). The structures of the new alkaloids were determined by extensive 1D and 2D NMR spectroscopic studies and X-ray diffraction.