Cyclic peptide conjugate of curcumin and doxorubicin as an anticancer agent

TETRAHEDRON LETTERS

卷:58

Article

Darwish, Shaban^1,2  Mozaffari, Saghar¹  Parang, Keykavous¹  Tiwari, Rakesh¹ 

[1] Chapman Univ, Sch Pharm, Ctr Targeted Drug Delivery, Dept Biomed & Pharmaceut Sci, Harry & Diane Rinker Hlth Sci Campus, Irvine, CA 92618 USA

[2] Natl Res Ctr, Organometall & Organometalloid Chem Dept, El Bohouth St, Giza, Egypt

关键词: Antiproliferative activity;    Combination therapy;    Curcumin;    Cyclic peptide;    Doxorubicin;   

DOI  :  10.1016/j.tetlet.2017.10.065

来源: Elsevier

【 摘 要 】

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, suggesting selectivity of these compounds towards cancer cells. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

Free