%0 Journal Article
%T Design and Synthesis of Novel Breast Cancer Therapeutic Drug Candidates Based upon the Hydrophobic Feedback Approach of Antiestrogens
%J Molecules | An Open Access Journal from MDPI
%D 2019
%R https://doi.org/10.3390/molecules24213966
%X Based upon hydrophobic feedback approaches, we designed and synthesized novel sulfur-containing ER¦Á modulators ( 4 and 5) as breast cancer therapeutic drug candidates. The tetrahydrothiepine derivative 5a showed the highest binding affinity toward ER¦Á because of its high hydrophobicity, and it acted as an agonist toward MCF-7 cell proliferation. The corresponding alkylamino derivative 5d maintained high binding affinity to ER¦Á and potently inhibited MCF-7 cell proliferation (IC 50: 0.09 ¦ÌM). Docking simulation studies of compound 5d with the ER¦Á BD revealed that the large hydrophobic moiety of compound 5d fit well into the hydrophobic pocket of the ER¦Á LBD and that the sulfur atom of compound 5d formed a sulfur¨C¦Ð interaction with the amino acid residue His524 of the ER¦Á LBD. These interactions play important roles for the binding affinity of compound 5d to the ER¦Á LBD. View Full-Tex
%U https://www.mdpi.com/1420-3049/24/21/3966