Document Type
Article
Publication Date
10-27-2017
Abstract
The hydrophobicity of curcumin creates hurdle towards its use in the anticancer therapy. Herein, we synthesized a curcumin-doxorubicin conjugated cyclic peptide scaffold to improve the solubility of curcumin and create a conjugate containing two anticancer agents. A solid-phase Fmoc/tBu solid phase methodology was used to synthesize a cell-penetrating nuclear targeting peptide with free thiol and amine groups, which was coupled with the activated doxorubicin (Dox) and curcumin, affording Dox-peptide-curcumin conjugate (DPCC) (10). The antiproliferative activity of the conjugate was evaluated in human leukemia carcinoma cell (CCRF-CEM), human ovarian carcinoma cell (SKOV-3), and normal kidney cell line (LLCPK). Cyclic peptide-doxorubicin conjugate (7) and DPCC (10) did not inhibit the proliferation of normal kidney LLCPK cells after 72 h incubation, but were cytotoxic in CCRF-CEM (73% and 41%, respectively) and SKOV-3 (55% and 30%, respectively) cells under similar conditions, suggesting selectivity of these compounds towards cancer cells while Dox was cytotoxic (60- 79%) in all three cell lines under similar conditions.
Recommended Citation
Darwish S, Mozaffari S, Parang K, Tiwari R. Cyclic peptide conjugate of curcumin and doxorubicin as an anticancer agent. Tetrahedron Lett. 2017;58(49):4617-4622. doi: 10.1016/j.tetlet.2017.10.065
Copyright
Elsevier
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Amino Acids, Peptides, and Proteins Commons, Cancer Biology Commons, Cell Biology Commons, Medicinal and Pharmaceutical Chemistry Commons, Other Pharmacy and Pharmaceutical Sciences Commons, Pharmaceutics and Drug Design Commons
Comments
NOTICE: this is the author’s version of a work that was accepted for publication in Tetrahedron Letters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version will subsequently be published in Tetrahedron Letters in 2017. DOI: 10.1016/j.tetlet.2017.10.065
The Creative Commons license below applies only to this version of the article.