TY - JOUR
T1 - A novel, dual action chimera comprising DNA methylating agent and near-IR xanthene-cyanine photosensitizer for combined anticancer therapy
AU - Thankarajan, Ebaston
AU - Walunj, Dipak
AU - Bazylevich, Andrii
AU - Prasad, Chandrashekhar
AU - Hesin, Arkadi
AU - Patsenker, Leonid
AU - Gellerman, Gary
N1 - Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
KW - Activatable anticancer prodrug
KW - Activatable photosensitizer
KW - Anticancer hybrid
KW - DNA methylation
KW - Fluorescence monitoring
UR - http://www.scopus.com/inward/record.url?scp=85123205336&partnerID=8YFLogxK
U2 - 10.1016/j.pdpdt.2022.102722
DO - 10.1016/j.pdpdt.2022.102722
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AN - SCOPUS:85123205336
SN - 1572-1000
VL - 37
JO - Photodiagnosis and Photodynamic Therapy
JF - Photodiagnosis and Photodynamic Therapy
M1 - 102722
ER -