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Synthesis of quinone methide precursors containing BODIPY fluorophore and characterization as potential anticancer drugs

Quinone methides (QMs) are reactive intermediates that have been shown as useful synthons in organic synthesis, 1 as well as biologically active agents applicable in biochemistry and medicine.1, 2 In the groups of S. Rokita3 and M. Freccero3 it has been demonstrated that QMs react with nucleotides and induce DNA alkylation and cross-linking, leading to cytotoxicity.5 The generation of QMs under mild conditions can be facilitated by photochemical dehydration6 and deamination, 7, 8 which are particularly interesting in biological systems.9 Consequently, photochemical generation of QMs may be developed into a new cancer phototreatment. To have molecules applicable in medicine, it is important to design new QM precursor molecules that have chromophores absorbing light at λ > 600 nm to assure penetration through tissues. Therefore, we incorporated BODIPY10 chromophore into the QM precursor units.11 For example BODIPY derivative 1 undergoes photodeamination and delivers QM that reacts with nucleophiles in a Michael addition. We have synthesized several BODIPY-QM precursors and investigated their photochemical reactivity and photophysical properties. Non-covalent interactions of BODIPY-QM precursors with DNA and proteins by several spectroscopic methods are investigated, as well as ability of photochemically formed QMs to covalently alkylate biomacromolecules.

BODIPY ; quinone methide ; photodeamination ; antiproliferative activity

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