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

Ebaston Thankarajan; Dipak Walunj; Andrii Bazylevich; Chandrashekhar Prasad; Arkadi Hesin; Leonid Patsenker; Gary Gellerman

doi:10.1016/j.pdpdt.2022.102722

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

Ebaston Thankarajan, Dipak Walunj, Andrii Bazylevich, Chandrashekhar Prasad, Arkadi Hesin, Leonid Patsenker, Gary Gellerman

Ariel University

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	102722
Journal	Photodiagnosis and Photodynamic Therapy
Volume	37
DOIs	https://doi.org/10.1016/j.pdpdt.2022.102722
State	Published - Mar 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Activatable anticancer prodrug
Activatable photosensitizer
Anticancer hybrid
DNA methylation
Fluorescence monitoring

All Science Journal Classification (ASJC) codes

Biophysics
Oncology
Dermatology
Pharmacology (medical)

Access to Document

10.1016/j.pdpdt.2022.102722

Cite this

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

abstract = "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.",

keywords = "Activatable anticancer prodrug, Activatable photosensitizer, Anticancer hybrid, DNA methylation, Fluorescence monitoring",

author = "Ebaston Thankarajan and Dipak Walunj and Andrii Bazylevich and Chandrashekhar Prasad and Arkadi Hesin and Leonid Patsenker and Gary Gellerman",

note = "Publisher Copyright: {\textcopyright} 2022 Elsevier B.V.",

year = "2022",

month = mar,

doi = "10.1016/j.pdpdt.2022.102722",

language = "الإنجليزيّة",

volume = "37",

journal = "Photodiagnosis and Photodynamic Therapy",

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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

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

M3 - مقالة

C2 - 35032703

SN - 1572-1000

VL - 37

JO - Photodiagnosis and Photodynamic Therapy

JF - Photodiagnosis and Photodynamic Therapy

M1 - 102722

ER -

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

Abstract

UN SDGs

Keywords

All Science Journal Classification (ASJC) codes

Access to Document

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