A highly GSH-sensitive SN-38 prodrug with an "OFF-to-ON" fluorescence switch as a bifunctional anticancer agent

SN-38 (7-ethyl-10-hydroxy-camptothecin) is an active metabolite of irinotecan (CPT-11) and the most potent camptothecin analogue. In this study, 2,4-dinitrobenzene sulfonyl (DNS) was covalently conjugated as a GSH-sensitive trigger to 10' -OH of SN-38 to yield a GSH-sensitive prodrug, denoted a...

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Bibliographic Details
Published in:Chemical communications (Cambridge, England) England), 2018-08, Vol.54 (65), p.931-934
Main Authors: Whang, Chang-Hee, Yoo, Eunsoo, Hur, Seong Kwon, Kim, Kyeong Soo, Kim, Dongin, Jo, Seongbong
Format: Article
Language:English
Subjects:
Animals
Anticancer properties
Antineoplastic Agents - chemistry
Antineoplastic Agents - metabolism
Antineoplastic Agents - pharmacology
Camptothecin - analogs & derivatives
Camptothecin - chemistry
Camptothecin - metabolism
Camptothecin - pharmacology
Cell Line, Tumor
Cell Nucleus - metabolism
Electron transfer
Fluorescence
Fluorescent Dyes - chemistry
Fluorescent Dyes - metabolism
Fluorescent Dyes - pharmacology
Glutathione - metabolism
Humans
Irinotecan
Kinetics
Mice
Microscopy, Confocal
Prodrugs - chemistry
Prodrugs - metabolism
Prodrugs - pharmacology
Restoration
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Summary:SN-38 (7-ethyl-10-hydroxy-camptothecin) is an active metabolite of irinotecan (CPT-11) and the most potent camptothecin analogue. In this study, 2,4-dinitrobenzene sulfonyl (DNS) was covalently conjugated as a GSH-sensitive trigger to 10' -OH of SN-38 to yield a GSH-sensitive prodrug, denoted as DNS-SN38, with virtually quenched fluorescence due to donor-excited photo-induced electron transfer (d-PeT). By investigating DNS-SN38's activation properties upon fluorescence restoration and cytotoxic potency against ovarian cancer cell lines (A2780 and m-Cherry + OCSC1-F2), its potential applicability as a useful chemotherapeutic agent was demonstrated. A DNS-SN38 prodrug that is capable of GSH-sensitive activation of quenched fluorescence for bifunctional application.
ISSN:1359-7345
1364-548X
DOI:10.1039/c8cc05010d