Synthesis of d- and l-tyrosine-chlorambucil analogs active against breast cancer cell lines

A series of d- and l-tyrosine-chlorambucil analogs was synthesized as anticancer drugs for chemotherapy of breast cancer. The novel compounds were synthesized in good yields through efficient modifications of d- and l-tyrosine. The newly synthesized compounds were evaluated for their anticancer efficacy in different hormone-dependent and hormone-independent (ER+ and ER−) breast cancer cell lines. The novel analogs showed significant in vitro anticancer activity when compared to chlorambucil. Structure–activity relationship (SAR) reveals both, the influence of the length of the spacer chain and the stereochemistry of the tyrosine moiety. Interestingly, the d- and l-tyrosinol-chlorambucil derivatives with 10 carbon atoms spacer are selective towards MCF-7 (ER+) breast cancer cell line.

Graphical abstractA series of d- and l-tyrosine-chlorambucil analogs is reported. The novel analogs showed significant in vitro anticancer activity when compared to chlorambucil on breast cancer cell lines. Some of the analogs showed selectivity towards MCF-7 (ER+) breast cancer cells.Figure optionsDownload full-size imageDownload as PowerPoint slide