engleski

Synthesis, photochemical reactivity and biological activity of a quinone methide precursors containing BODIPY chromophore - potential photoactive 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 It has been shown that QMs react with nucleotides and induce DNA alkylation and cross-linking, leading to cytotoxicity.3-5 The generation of QMs under mild conditions can be facilitated by photochemical elimination reactions.6-9 On the other hand, BODIPY derivates are commonly used as dyes for biomolecular labeling since they are characterized by good photochemical stability and excellent photophysical and spectral properties.10 To obtain desired photochemical properties and biological activity and develop potential photoactivable anticancer drug we incorporated BODIPY chromophore into the QM precursor units.11 BODIPY-QM precursor molecules 1-4 have been synthesized in the multi step synthetic pathway that includes condensation of an aldehyde and pyrrole, synthesis of BODIPY core and funtionalisation using chlorination, Suzuki and Mannich reaction. Synthesized precursor molecules 1-4 undergoes photodeamination reactions and delivers QM that reacts with nucleophiles in a Michael addition. Non-covalent interactions of BODIPY-QM precursors with biomacromolecules as well as ability of photochemically formed QMs to covalently alkylate biomacromolecules were investigated. Furthermore, antiproliferative activity of synthesized BODIPY-QM precursors was investigated using MTT assay on several cell lines with and without irradiation.

photodeamination ; BODIPY ; quinone methide ; protein labeling ; photoactive anticancer drugs

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