Synthesis of new fatty acid derivatives of oleanane and ursane triterpenoids and investigation of their in vitrocytotoxic effects on 3T3 fibroblast and PC3 prostate cancer cell lines

Özet

In this study, 12 new oleanane and ursane derivative triterpene compounds,havingfatty acids in the form of esters with carbon numbers of 12, 13, 18, 19, 24 and 25,were synthesized starting from naturalproductsoleanolic and ursolic acids. Initially,3-methylerythrodiol (3β-methoxyolean-12-en-28-ol) and 3-methyluvaol(3β-methoxyurs-12-en-28-ol) were synthesized from oleanolic acid and ursolic acid,respectively. For this purpose,secondary OH group at C-3 of oleanolic and ursolic acidswereprotected as methyl ether and,then,theircarboxylic acidmoietieswere reduced by aluminum hydride. New fatty acid derivatives5a-fand 8a-fwere synthesized through thereaction of 3-methylerythrodiol/3-methyluvaol and corresponding fatty acid halides. In vitrocytotoxic activitiesof the all synthesized compoundswere investigated on 3T3 fibroblast cells and PC3 prostate cancer cell lines. While all the compounds showedat least 70% inhibition on PC3 prostate cancer cells at a concentration of 25 μM, theyhadaverage of 50% inhibition on 3T3 fibroblast human healthy cells at the same concentration. Compounds5cand 8cdemonstrated the least toxic effect on 3T3 fibroblast human healthy cells and the highest toxic effect on PC3 prostate cancer cellsat a concentration of 12.5 μM.Moreover, compounds 8cand 8ehad the least toxic effect on 3T3 fibroblast human healthy cells and the highest toxic effect on PC3 prostate cancer cells at the same concentration.