Evaluation of the cytotoxic potential of catechols and quinones structurally related to butylated hydroxyanisole.
The cytotoxicity of 2- and 3-butylated hydroxyanisole (BHA) and 18 related aromatic compounds has been determined employing cultured P388 and KB cells. The phenolic compounds, 3-BHA and 2-BHA, had moderately low cytotoxic activity. Their corresponding catechols had ED50 values that were much lower than those of the parent compounds. This substantial increase in the cytotoxic activity is attributed to the presence of the catechol group, which is known to undergo one-electron oxidation readily to give the corresponding semiquinone radical. Other related catechols had similar cytotoxic activity. In general, derivatization of the catechol functionality resulted in a decrease of the cytotoxic potential of the compounds. Monoacetylation or monomethylation of the catechols gave products that were less potent cytotoxic agents than the parent compounds. Further loss of activity was observed when both hydroxy groups of the catechol function were blocked. Substitution of a methoxy group in place of a hydrogen atom in these compounds resulted in a significant increase of cytotoxicity, whereas the replacement of a methoxy group with a methyl group reduced the cytotoxicity. The catechols and quinones derived from 2-BHA were more active when compared with those derived from 3-BHA. The t-butyl group adjacent to the catechol or quinone moiety in the 3-BHA derivatives appeared to exert a significant steric effect toward the cytotoxic potential of these compounds. These results suggest the potential use of o-quinones and catechols as cytotoxic and antitumor agents.
Lam
L K
LK
Gray Freshwater Biological Institute, University of Minnesota, Navarre 55392.
Garg
P K
PK
Swanson
S M
SM
Pezzuto
J M
JM
D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D002396:Catechols / Q000138:chemical synthesis / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects*; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D011809:Quinones / Q000138:chemical synthesis / Q000494:pharmacology*
D002396:Catechols; D011809:Quinones; D002083:Butylated Hydroxyanisole