Naslov
ANTIPROLIFERATIVE ACTIVITY OF PHOTOGENERATED QUINONE METHIDES FROM ANTHRACENE DERIVATIVES

Autori
Basarić, Nikola ; Škalamera, Đani ; Mlinarić- Majerski, Kata ; Kralj, Marijeta ; Uzelac, Lidija ; Martin-Kleiner, Irena ; Wang, Yu-Hsuan ; Wan, Peter

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
XXV IUPAC Symposium on Photochemistry / - Bordeaux, 2014, OC45-OC45

Skup
XXV IUPAC Symposium on Photochemistry

Mjesto i datum
Bordeaux, Francuska, 13.07.2014. - 18.07.2014

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Antiproliferative activity; Anthracene derivatives; Photogenerated QMs; Quinone methides (QMs);
(Antiproliferative activity; Anthracene derivatives; Photogenerated QMs; Quinone methides (QMs))

Sažetak
Quinone methides (QMs) are important reactive intermediates that have attracted significant scientific interest owing to their reactivity with DNA [1] and proteins [2]. QMs can be photogenerated under mild conditions, enabling spatial and temporal control of the process, which is particularly applicable to biological systems. Moreover, it has been demonstrated that QMs generated in the photo-dehydration or photo- deamination reactions induce antiproliferative action in human cancer cell lines [3]. However, for real biological applications, QMs should be photogenerated with visible or near IR light. Herein, we report investigation of photochemical reactivity of two series of anthracene derivatives that on excitation with near-visible light (λ > 350 nm) give QMs. The first series of compounds are 2-anthrol derivatives 1a-1d that undergo photo-dehydration or photo-deamination, 1e [4]. The second generation of compounds are (2- hydroxyphenyl)anthracene derivatives 2a-2d that undergo excited state intramolecular proton transfer (ESIPT) from the phenolic OH to the anthracene carbon atom [5]. Both types of photochemical reactions give QMs that have been detected by laser flash photolysis. Moreover, preparative photolyses in the presence of biological nucleophiles were conducted to demonstrate the ability of QMs to react as electrophiles. Antiproliferative activity of the photogenerated QMs was investigated on three tumor cancer cell lines (colon HCT 116, breast MCF-7, and lung H 460), with and without exposure of cells to irradiation (350nm and 420 nm and white light). The mechanism of the antiproliferative action was studied in more detail with compound 2a, by performing investigation of non-covalent binding to DNA and irradiations of plasmid DNA in the presence of 2a, followed by the analysis by alkaline gel electrophoresis. Moreover, a study of the influence of 2a on the cell cycle of HCT 116 cells indicated that photogenerated QM caused a strong reduction in the number of cells in the S phase and induced both G1 and G2/M phase arrest, and significantly increased the number of apoptotic cells, while without irradiation, 2a negligibly influences the cell cycle. However, these and other additional experiments indicate that the compound does not react with DNA, but probably interacts with other cellular target(s). These new findings open new possibilities in the design of compounds for anticancer photo-therapy based on photogeneration of QMs.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA