The potential hepatotoxic effects of compound 5i can be attributed to furan ring oxidation as multiple hydroxylation of the compound was determined (data not shown). Depending on the substituents on the furan ring, the intermediate is either an epoxide or a cis-enedione . Since the 2-position of the furan ring is blocked by a methyl group and the 5-position is occupied by the THA scaffold, epoxide formation is less likely, while the formation of a cis-enedione is more probable. For derivative 5m, the thiophene ring will likely to undergo P450-catalyzed hydroxylation at the carbon atoms adjacent to the sulfur atom, forming of 2-hydroxythiophene. However, from the obtained, the oxidation site can only be speculated. According to the literature, it is also possible that the thiophene can be oxidized to unstable and reactive thiophene-S-oxide metabolites .