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Open AccessArticle

Synthesis and Cytotoxicity of 7,9-O-Linked Macrocyclic C-Seco Taxoids

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 2A Nan Wei Road, Beijing 100050, China
Department of Biomedical Sciences and “Unidad Asociada IQM-CSIC”, School of Medicine and Health Sciences, University of Alcalá, E-28805 Alcalá de Henares, Madrid, Spain
Author to whom correspondence should be addressed.
Academic Editor: Qiao-Hong Chen
Molecules 2019, 24(11), 2161;
Received: 23 May 2019 / Revised: 5 June 2019 / Accepted: 6 June 2019 / Published: 8 June 2019
(This article belongs to the Special Issue Anticancer Agents: Design, Synthesis and Evaluation)
A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated. It is demonstrated that C-seco taxoids conformationally constrained via carbonate containing-linked macrocyclization display increased cytotoxicity on drug-resistant tumors overexpressing both βIII and P-gp, among which compound 22b, bearing a 2-m-methoxybenzoyl group together with a five-atom linker, was identified as the most potent. Molecular modeling suggested the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII. View Full-Text
Keywords: taxoids; βIII-tubulin; P-glycoprotein; drug resistance taxoids; βIII-tubulin; P-glycoprotein; drug resistance
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MDPI and ACS Style

Zhao, Y.; Wang, T.-E.; Mills, A.; Gago, F.; Fang, W.-S. Synthesis and Cytotoxicity of 7,9-O-Linked Macrocyclic C-Seco Taxoids. Molecules 2019, 24, 2161.

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