Design, synthesis and biological evaluation of estradiol–chlorambucil hybrids as anticancer agents

The synthesis of a series of estradiol–chlorambucil hybrids is reported. The hybrids showed significant in vitro anticancer activity when compared to chlorambucil on breast cancer cell lines. A series of estradiol–chlorambucil hybrids was synthesized as anticancer drugs for site-directed chemotherapy of breast cancer. The novel compounds were synthesized in good yields through efficient modifications of estrone at position 16α of the steroid nucleus. The newly synthesized compounds were evaluated for their anticancer efficacy in different hormone-dependent and hormone-independent breast cancer cell lines. The novel hybrids showed significant in vitro anticancer activity when compared to chlorambucil. Structure–activity relationship (SAR) reveals the influence of the length of the spacer chain between carrier and drug molecule.