Nucleoterpenoids consisting of isosteviol and uridine. Synthesis and cytotoxicity evaluation

A series of nucleoterpenoids in which uridine is attached to diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) by means of an alkyl or 1,2,3-triazolylalkyl linker has been synthesized. Screening of their in vitro cytotoxicity against 7 cancer cell lines revealed three lead compounds. This is nucleoterpenoid 13c in which the uridine moiety is attached by the octyl linker to the amide group of isosteviol. Compound 13c caused the death of MCF-7 and PANC-1 cancer cells at an IC50 concentration of 11 µM. Nucleoterpenoid 15b, in which the uridine moiety with protected hydroxyl groups is attached by the 1,2,3-triazolylbutyl linker to the C-16(S) position of isosteviol, caused the death of cancer cells M-HeLa, MCF-7, PANC-1, PC-3, A 549, and HuTu 80 at IC50 values in the range 10.4–16.8 µM. Its derivative, nucleoterpenoid 15d with free hydroxyl groups, caused the death of cancer cells MCF-7, PANC-1, PC-3, and A 549 at IC50 values in the range 11.7–19.5 µM.