Antimalarial, antimycobacterial and antiproliferative activity of phenyl substituted mixed tetraoxanes

Abstract

Mixed tetraoxanes of the 4"-phenyl-substituted cyclohexyl-spirotetraoxacyclohexyl- spirocholate series have been prepared and evaluated as possible antimalarials, antiproliferatives and antimycobacterials. The activity of the (4"R or S)-phenyl series against P. falciparum D6 and W2 strains was found to be at the level of artemisinin with two compounds, the acid 4 and the amide 6, exhibiting encouraging anti-TB activity as well. Very promising in vitro results of the said tetraoxanes were obtained against solid tumours and, in some instances, the activity against a selected number of cell lines was higher than that of the antitumor drug Paclitaxel.

U ovom radu prikazana je sinteza serije mešovitih tetraoksana 4"-fenil-supstituisanih cikloheksil-spirotetraoksacikloheksil-spiroholata, a ispitana je i njihova in vitro aktivnost kao mogućih antimalarika, anti-TBC agenasa i antiproliferativnih jedinjenja. Aktivnost (4"R ili S)-fenil serije na D6 i W2 sojeve P. falciparum vrlo je slična aktivnosti poznatog antimalarika artemizinina. Izraženu anti-TBC aktivnost iskazala su jedinjenja 4 i 6, čija antiproliferativna in vitro aktivnost prema nekim kompaktnim tumorima prevazilazi aktivnost leka paklitaksela.