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Synthesis and Cytotoxicity of 7,9-O-Linked Macrocyclic C-Seco Taxoids
- Source :
- Molecules, Vol 24, Iss 11, p 2161 (2019)
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 2019.
-
Abstract
- 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.
- Subjects :
- taxoids
βIII-tubulin
P-glycoprotein
drug resistance
Organic chemistry
QD241-441
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 24
- Issue :
- 11
- Database :
- Directory of Open Access Journals
- Journal :
- Molecules
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.f34f4b2edfe445688bba7b16ea5256e2
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/molecules24112161