RESUMO
A range of 11 derivatives of flavone-8-acetic acid (FAA) in which the structure has been substantially altered in different ways have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. The generally poor activity observed shows that the basic structure cannot be altered much without destroying the activity.
Assuntos
Antineoplásicos/síntese química , Flavonoides/síntese química , Animais , Antineoplásicos/farmacologia , Flavonoides/farmacologia , Humanos , Camundongos , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
A range of 14 derivatives of flavone-8-acetic acid (FAA) with a heterocyclic substituent in place of the 2-phenyl group have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. Some of the compounds, notably 2c,d and s, showed significant in vivo activity and these require further studies in order to evaluate their potential for development.
Assuntos
Antineoplásicos/síntese química , Flavonoides/síntese química , Flavonoides/farmacologia , Compostos Heterocíclicos/síntese química , Animais , Antineoplásicos/farmacologia , Compostos Heterocíclicos/farmacologia , Humanos , Camundongos , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Células Tumorais CultivadasRESUMO
A range of 18 derivatives of flavone-8-acetic acid (FAA) with substituents on the 2-phenyl group have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. There was no clear-cut relationship between in vitro and in vivo activity but the activity in each situation was found to be very sensitive to the precise substitution pattern with closely related isomers giving widely different activities. Some of the compounds, notably 10b,c,j, and r, were active in vivo and these require further studies in order to evaluate their potential for development.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Flavonoides/síntese química , Flavonoides/farmacologia , Animais , Neoplasias do Colo/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
5,6-Dimethylxanthenone-4-acetic acid (5,6-MeXAA) is a fused tricyclic analogue of flavone acetic acid (FAA) which was developed in an attempt to improve on the activity of FAA. Previous studies have shown 5,6-MeXAA to be curative in 80% of mice bearing colon 38 tumours and 12 times more dose potent than FAA. This investigation has demonstrated that a murine colon tumour cell line (MAC15A) is approximately 60 times more sensitive to 5,6-MeXAA than to FAA, although these differences were not seen in three human cell lines tested. 5,6-MeXAA caused significant blood flow shutdown and haemorrhagic necrosis in subcutaneous MAC15A tumours in syngeneic and nude hosts, but measurable changes in tumour volume were seen only in syngeneic hosts. 5,6-MeXAA was inactive against intraperitoneal MAC15A but produced significant anti-tumour effects against the same cell line inoculated via an intravenous route. FAA has been shown previously to be inactive in this model. Interestingly, the effects against lung colonies were not accompanied by obvious necrotic changes, suggesting that they may be the result of increased direct cytotoxicity rather than an indirect host mechanism. Further studies to investigate the effects against systemic tumour deposits are under way.
