Isolation and identification of two pairs of cytotoxic diterpene tautomers and their tautomerization mechanisms

Abstract

Discovering anticancer drugs that do not have adverse side effects has been a developing research field worldwide in recent decades. In this work, four previously undescribed cytotoxic diterpenoids were isolated from the aerial parts of Isodon excisoides. Interestingly, these four diterpenoids were two pairs of tautomers that were first reported in plants. Their structures were further elucidated using various spectroscopic methods. The tautomerization phenomenon and mechanism for these two pairs of tautomers were emphatically described. The theoretical simulation results indicated that the diterpene tautomerization is greatly related to certain factors, including the existence of a transition state, the change of bond length and the level of conversion energy; the tautomerization for the two pairs of tautomers is mainly caused by proton transfer. For bioassays, the cytotoxicities of the tautomers against five human cancer cell lines were also investigated. The results indicated that each of the four diterpenoids showed significant cytotoxicity in at least three cell lines and could serve as potential anticancer agents for further investigation.