Synthesis, Aromatase Inhibition, Cytotoxicity and Molecular Docking Studies of New Fluorinated and Non‐Fluorinated Thiourea Derivatives of Desloratadine

Aromatase inhibitors are among the most effective treatment of the breast cancer. Aromatase catalyzes estrogen biosynthesis, which is a long-term cause of breast cancer. Current study describes the synthesis, purification of 26 new fluorinated and non-fluorinated thiourea derivatives of desloratadine (5), and their aromatase inhibition activity, cytotoxicity against cancer cell line (MDA-MB-231). Compounds 7 v and 7 l exhibited a significant anti-aromatase activity, while compounds 7 a, 7 g-h, 7 m and 7 u were also significant active against MDA-MB-231 cell line. Furthermore, the molecular docking studies revealed that active compounds form key interactions with the crucial amino acid of aromatase active site including TRP224, LEU477, CYS437, ALA438, MET374, ARG115, ILE305, and PHE221, which are responsible for the binding interactions of aromatase. All analogues were new, except 7 b and 7 k and also lacked cytotoxicity against BJ human fibroblasts, with the exception of 5 and 7 x. This selectivity makes this series particularly interesting for further studies.