Furanolabdanoid–based 1,2,4‐oxadiazoles: Synthesis and cytotoxic activity

AbstractSeveral 15,16‐epoxy‐8,13,14‐labdatriene derivatives modified at the C‐16 position with a 1,2,4‐oxadiazole ring with various substituent in the 5‐th position, were obtained via multistep synthesis from 16‐formyl derivatives of natural diterpenoid lambertianic acid. The cytotoxicity of furanolabdanoid‐based 1,2,4‐oxadiazoles was evaluated against human cancer cells (CEM‐13, MT‐4, U‐937, MCF‐7, MDA‐MB‐231, MEL‐8) using the conventional MTT assays. All the tested diterpenoid‐oxadiazole hybrids displayed better cytotoxic activity then lambertianic acid. The activity and selectivity to the cell line increased even further in the compounds containing a chloromethyl substituent in the 5‐th position of the 1,2,4‐oxadiazole ring. Two of the synthesized compounds exhibited high cytotoxic activity against lymphoblastoid cell line CEM‐13 (GI500.08‐0.34 μM), which was higher that than of the comparative drug Doxorubicin. The antitumor mechanism may be related to apoptosis induction in U‐937, MCF‐7, and CEM‐13 cells.