國家衛生研究院 NHRI:Item 3990099045/14115

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/14115

Title:	Click chemistry and multicomponent reaction for linker diversification of zinc dipicolylamine-based drug conjugates
Authors:	Tsai, CH;Chiu, TY;Chen, CT;Hsu, CY;Tsai, YR;Yeh, TK;Huang, KH;Tsou, LK
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	An efficient Ugi multicomponent reaction with strain promoted azide-alkyne cycloaddition protocol has been utilized in concert or independently to prepare a small family of bioactive zinc(II) dipicolylamine (ZnDPA)-based SN-38 conjugates. With sequential click chemistry coupling between the cytotoxic payload and phosphatidylserine-targeting ZnDPA ligand derived from structurally diverse carboxylic acids, aldehyde or ketones, and isocyanides, we demonstrated that this convergent synthetic strategy could furnish conjugates harnessing diversified linkers that exhibited different pharmacokinetic profiles in systemic circulation in vivo. Among the eight new conjugates, comparative studies on in vitro cytotoxicities, plasma stabilities, in vivo pharmacokinetic properties, and maximum tolerated doses were then carried out to identify a potent ZnDPA-based SN-38 conjugate that resulted in pancreatic cancer growth regression with an 80% reduction of cytotoxic payload used when compared to that of the marketed irinotecan. Our work provided the roadmap to construct a variety of theranostic agents in a similar manner for cancer treatment.
Date:	2022-02-15
Relation:	Frontiers in Chemistry. 2022 Feb 15;9:Article number 822587.
Link to:	http://dx.doi.org/10.3389/fchem.2021.822587
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2296-2646&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000798696100001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85125561740
Appears in Collections:	[Lun Kelvin Tsou] Periodical Articles [Teng-Kuang Yeh] Periodical Articles [Chiung-Tong Chen] Periodical Articles

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