engleski

Competing photochemical reactions of bis-naphthols and their photoinduced antiproliferative activity

Photophysical properties and photochemical reactivity for a series of bis-naphthols 4a-4e and bis-anthrols 5a and 5e were investigated by preparative irradiations in CH3OH, fluorescence spectroscopy and laser flash photolysis (LFP). Methanolysis taking place via photodehydration (bis-naphthols ΦR = 0.04-0.05) is in competition with symmetry breaking charge separation (SB- CS). The SB-CS gives rise to radical ions that were for 4a and 4e detected by LFP. Photodehydration gives quinone methides (QMs) that were also detected by LFP (λmax = 350 nm, τ ≈ 1-2 ms). In the aqueous solvent, excited state proton transfer (ESPT) competes with the above mentioned processes, giving rise to naphtholates, but the process is inefficient and can only be observed in the buffered aqueous solution at pH >7. Since the dehydration of bis- naphthols delivers QMs, their potential antiproliferative activity was investigated by MTT test on three human cancer cell lines (NCI- H1299, lung carcinoma ; MCF-7, breast adenocarcinoma ; and SUM159, pleomorphic breast carcinoma). Cells were treated with 4 or 5 with or without irradiation (350 nm). An enhancement of the activity (up to 10-fold) was observed upon irradiation, which may be associated to the QM formation. However, these QMs do not cross- link DNA. The activity is most likely associated to the alkylation of proteins present in the cell cytoplasm, as evidenced by photoinduced alkylation of bovine and human serum albumins by 4a.

Naphthols ; photodehydration ; quinone methides ; antiproliferative activity ; DNA cross-linking ; photoinduced electron transfer ; protein alkylation

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