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-cyan...

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Veröffentlicht in:	Photodiagnosis and photodynamic therapy 2022-03, Vol.37, p.102722-102722, Article 102722
Hauptverfasser:	Thankarajan, Ebaston, Walunj, Dipak, Bazylevich, Andrii, Prasad, Chandrashekhar, Hesin, Arkadi, Patsenker, Leonid, Gellerman, Gary
Format:	Artikel
Sprache:	eng
Schlagworte:	Activatable anticancer prodrug Activatable photosensitizer Anticancer hybrid Cell Line, Tumor Chimera DNA - chemistry DNA methylation Fluorescence monitoring Humans Photochemotherapy - methods Photosensitizing Agents - pharmacology Xanthenes - chemistry
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container_title	Photodiagnosis and photodynamic therapy
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creator	Thankarajan, Ebaston Walunj, Dipak Bazylevich, Andrii Prasad, Chandrashekhar Hesin, Arkadi Patsenker, Leonid Gellerman, Gary
description	•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]
doi_str_mv	10.1016/j.pdpdt.2022.102722
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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. 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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. 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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. 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subjects	Activatable anticancer prodrug Activatable photosensitizer Anticancer hybrid Cell Line, Tumor Chimera DNA - chemistry DNA methylation Fluorescence monitoring Humans Photochemotherapy - methods Photosensitizing Agents - pharmacology Xanthenes - chemistry
title	A novel, dual action chimera comprising DNA methylating agent and near-IR xanthene-cyanine photosensitizer for combined anticancer therapy
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