Fatty Acyl Amide Dderivatives of Doxorubicin: Synthesis and In Vitro Anticancer Activities

Authors

Bhupender S. Chhikara, University of Rhode Island
Nicole St. Jean, University of Rhode Island
Deendayal Mandal, University of Rhode IslandFollow
Anil Kumar, Birla Institute of Technology and Science (BITS)Follow
Keykavous Parang, Chapman UniversityFollow

Document Type

Article

Publication Date

2011

Abstract

Doxorubicin is an anticancer drug extensively used in anticancer therapy. Doxorubicin is highly hydrophilic, has short half-life, and its use is associated with severe side effects at high doses. Fatty acyl amide derivatives of doxorubicin were synthesized with the expectation to improve the lipophilicity and anticancer activity of the drug. The lipophilicity was enhanced with the increase in chain length of fatty acyl moiety. Conjugation of 4-amino group with fatty acids through an amide bond reduced the anticancer activity in leukemia, breast, ovarian, and colon cancer cell lines, suggesting that the presence of free amino group is required for anticancer activity of doxorubicin. Dodecanoyl-doxorubicin derivative was consistently the most effective among the synthesized derivatives and inhibited the proliferation of colon (HT-29) and ovarian (SK-OV-3) cancer cells by 64% and 58%, respectively, at a concentration of 1 µM after 96 h incubation.

Comments

NOTICE: this is the author’s version of a work that was accepted for publication in European Journal of Medicinal Chemistry. 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 was subsequently published in European Journal of Medicinal Chemistry, volume 46, issue 6, in 2011. DOI: 10.1016/j.ejmech.2011.02.056

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Recommended Citation

Chhikara, Bhupender S., et al. "Fatty acyl amide derivatives of doxorubicin: Synthesis and in vitro anticancer activities." European journal of medicinal chemistry 46.6 (2011): 2037-2042. doi: 10.1016/j.ejmech.2011.02.056

Copyright

Elsevier

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.