RESUMO
A series of quinopimaric and maleopimaric acids' derivatives modified in the E-ring, at the carbonyl- and carboxyl-groups were synthesized and their in vitro cytotoxic activity was evaluated at the National Cancer Institute, USA. Methyl esters of dihydroquinopimaric, 1a,4a-dehydroquinopimaric, 2,3-epoxyquinopimaric, 1-ethylenketal-dihydroquinopimaric, 1-ethylenketal-4-hydroxyiminodihydroquinopimaric acids displayed an activity on renal cancer, leukemia, colon cancer and breast cancer cell lines in concentration 10(−5) M. Methyl 1,4-dihydroxyiminodihydroquinopimarate showed both a potent and broad spectrum of cytotoxic activity against NSC lung cancer, colon cancer, breast cancer, renal cancer and leukemia and revealed in vivo antineoplastic activity towards mouse solid transplantable mammary carcinoma Ca755 and colon adenocarcinoma AKATOL. The information about antineoplastic activity of the studied quinopimaric and maleopimaric acids' derivatives will be used for hit to lead optimization in these chemical series.
Assuntos
Antineoplásicos/síntese química , Diterpenos/química , Triterpenos/química , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/síntese química , Diterpenos/toxicidade , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Relação Estrutura-Atividade , Triterpenos/síntese química , Triterpenos/toxicidadeRESUMO
Mussels and tunicates cultivated in Mediterranean and Black Sea are the sources of antitumor drugs. Three compounds isolated from these animals (ET-743, aplidin and bryostatin-1) are on the II-III stages of clinical trials. Carotenoid fucoxantin that is present in edible brown algae possesses antitumor activity. The consumption of brown macrophyts decreases the risk of cancer development.
