Authors: Darwish, Shaban; Mozaffari, Saghar; Parang, Keykavous; Tiwari, Rakesh; Tetrahedron Letters; (2017); 10.1016/j.tetlet.2017.10.065
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 while Dox was cytotoxic (60–79%) in all three cell lines under similar conditions, suggesting selectivity of these compounds towards cancer cells.