A novel, dual action chimera comprising DNA methylating agent and near-IR xanthene-cyanine photosensitizer for combined anticancer therapy

•Dual action anticancer molecular chimeras XCy and I-XCy are developed.•DNA methylating azene moiety is bound to activatable xanthene-cyanine photosensitizer.•These core structures are linked by self-immolative 4-aminobenzyl alcohol linker.•XCy and I-XCy enable both DNA methylation and xanthene-cyanine induced phototoxicity.•I-XCy exhibits higher combined antitumor activity upon near-IR light irradiation. A facile synthesis, biological evaluation and photodynamic properties of novel activatable anticancer molecular hybrids (chimeras) Ch and I-Ch are described. The chimeras consist of DNA methylating methyl triazene moiety and fluorogenic xanthene-cyanine (XCy) or iodinated xanthene-cyanine (I-XCy) photosensitizer. These two anticancer core structures are bound by means of a self-immolative 4-aminobenzyl alcohol linker. The hydrolytic cleavage of the carbamate protecting group promotes activation of both DNA methylating monomethyl triazene and phototoxic xanthene-cyanine dye providing, in addition, a near-IR emission signal for detection of the drug activation events. Preliminary antiproliferative assay demonstrates that the developed chimeras exhibit higher antitumor activity in the breast cancer cell line upon near-IR light irradiation compared to their structural constituents, xanthene-cyanine photosensitizer and monomethyl triazene substance. [Display omitted]