Sterically congested quinone methides in photodehydration reactions of 4-hydroxybiphenyl derivatives and investigation of their antiproliferative activity.
|
| Abstract |
In aqueous media, photochemical excitation (S(1)) of hydroxyadamantyl, diphenylhydroxymethyl, and hydroxypropyl derivatives of 4-phenylphenol 5-9 leads to solvent-assisted deprotonation of the phenol OH, and protonation of the benzyl alcohol coupled with dehydration, that delivers quinone methides (QMs) 14-18. The QMs react with CH(3)OH converting them in high quantum yields to the photosolvolysis products (overall Φ∼ 0.1-0.5). QMs were characterized by laser flash photolysis in CH(3)CN-H(2)O and TFE. In TFE, the zwitterionic QM 15 has a lifetime of 250 ns, whereas para QMs 16 and 17 have lifetimes of 500 μs and 1.1 s, respectively. Introduction of the steric hindrance to the parent QM structure (with the adamantyl moiety), or additional stabilization by two phenyl rings, results in an increase of QM lifetimes and selectivity in the reactions with nucleophiles. In vitro studies of the antiproliferative activity of photochemically generated QMs 15-17 were carried out on one human cancer cell line. Irradiation of cells incubated with 7 showed enhanced antiproliferative activity compared to cells that were not irradiated, in accordance with the activity being due to the formation of QM 16.
|
|---|---|
| Authors | Nikola Basarić, Nikola Cindro, Damir Bobinac, Kata Mlinarić-Majerski, Lidija Uzelac, Marijeta Kralj, Peter Wan |
| Journal | Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology (Photochem Photobiol Sci) Vol. 10 Issue 12 Pg. 1910-25 (Dec 2011) ISSN: 1474-9092 [Electronic] England |
| PMID | 22008723 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!