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

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Abstract

The photophysical properties and photochemical reactivities of a series of bis-naphthols 4a–4e and bis-anthrols 5a and 5e were investigated by preparative irradiation 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 gave rise to radical ions that were detected for 4a and 4e by LFP. Photodehydration gave 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 abovementioned 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 an 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 with QM formation. However, these QMs do not cross-link DNA. The activity is most likely associated with the alkylation of proteins present in the cell cytoplasm, as evidenced by photoinduced alkylation of bovine and human serum albumins by 4a.

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Authors and Affiliations

  1. Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10 000, Zagreb, Croatia

    Matija Sambol & Nikola Basarić

  2. Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10 000, Zagreb, Croatia

    Katja Ester, Mario Cindrić & Marijeta Kralj

  3. Institute of Physical and Theoretical Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010, Graz, Austria

    Stephan Landgraf

  4. Division of Materials Chemistry, Ruđer Bošković Institute, Zagreb, Croatia

    Branka Mihaljević

  5. Fidelta Ltd, Prilaz baruna Filipovića 29, 10000, Zagreb, Croatia

    Matija Sambol

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Electronic supplementary information (ESI) available: Synthetic procedures, fluorescence and LFP data, noncovalent binding to albumins, mass spectra measured by MALDI-TOF/TOF of BSA and HSA after photochemical alkylation, DNA cross-linking and antiproliferative data, 1H and 13C NMR spectra for all new compounds. See DOI: 10.1039/c8pp00532j

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Sambol, M., Ester, K., Landgraf, S. et al. Competing photochemical reactions of bis-naphthols and their photoinduced antiproliferative activity. Photochem Photobiol Sci 18, 1197–1211 (2019). https://doi.org/10.1039/c8pp00532j

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