Teprenone conjugated with a planar catechin analog enhances cytotoxicity against cancer cells.

Catechin is a natural compound abundant in green tea and is known as an antioxidant. We previously synthesized a catechin analog with a planar structure (planar catechin, PCat) and reported that it has about 10-fold stronger radical-scavenging activity than the parental (+)-catechin. We also showed that chemical conjunction of two different types of antioxidants has the potential to create an efficient antioxidant network for scavenging reactive oxygen species. In this study, we synthesized a PCat conjugated with teprenone (Tep), which is also known as a potential antioxidant, and found that the PCat-Tep conjugate exhibited remarkable cytotoxicity in cancer cells. On the other hand, the scavenging activity toward superoxide anion and DNA-protective effect against X-ray irradiation in aqueous solution were not enhanced by Tep conjugation. However, kinetic analysis of radical-scavenging activity in an organic solvent indicated that the PCat-Tep conjugate was approximately twice as effective as PCat alone. Moreover, the results of quantum chemical calculations imply that the association of subtle kinetic effects, such as differences in reorganization energy, solvation, or steric and conformational factors arising from the long hydrophobic side chain, rather than thermodynamic factors, are associated with the reactivity of the PCat-Tep conjugate.