Synthesis and Evaluation of Apoptotic Induction of Human Cancer Cells by Ester Derivatives of Thujone
Medicinal Chemistry Research
Thujone (1), thujol (2), and aromatic thujol esters (3–9) were evaluated for their ability to induce cell death in human cervical (HeLa), melanoma (A375), and colon (HCT-116) cancer cell lines, using etoposide as a positive control. The compounds showed dose-dependent activity at concentrations ranging from 50–400 μg/mL. Etoposide exhibited an IC50 value of 116 μg/ mLin HeLa cells, and α-thujone, α/β-thujone (7:1), and thujol showed comparable activity with IC50 values of 191, 198, and 1234567890();,: 1234567890();,: 136 μg/mL, respectively. All seven ester derivatives were cytotoxic to HeLa and HCT-116 cells, while a subset was cytotoxic to A375 cells. In HeLa cells, t-cinnamate (4), t-isonicotinate (5), t-nicotinate (6), and t-furoate (8) were more potent than either α-thujone or α/β-thujone. Similarly, t-furoate (8) was more potent than thujone in A375 cells, and t-isonicotinate (5) and t-nicotinate (6) were more potent against HCT-116 cells. Based on cell morphology, PARP cleavage and an increase in the caspase-3/7 levels, the esters exert their cytotoxic effects by induction of apoptosis.
Castner, E., Dickson, M., Mykytyn, A. et al. Synthesis and evaluation of apoptotic induction of human cancer cells by ester derivatives of thujone. Medicinal Chemistry Research 29, 268–280 (2020). https://doi.org/10.1007/s00044-019-02481-8