NEW ESTROGEN-NITROSOUREA DERIVATIVE AS AN ANTINEOPLASTIC DRUG CANDIDATE: EVALUATION OF IN SILICO PROPERTIES, MOLECULAR DOCKING AND PROPOSED SYNTHESIS

Abstract

The expression of estrogen receptor α (ERα) in breast cancer suggested the steroid-alkylating conjugation to improve antineoplastic therapy. Thus, platinum complexes linked to estrogen via Cu(I) azide-alkyne click chemistry showed in vitro cytotoxicity superior to cisplatin, and steroid-nitrosourea conjugates demonstrated promising results. However, no attempts were found to synthesize steroid-nitrosourea conjugates using click chemistry. Therefore, this study aims to predict, in silico, physicochemical, pharmacokinetic, and drug-likeness properties, perform molecular docking with ERα, and propose the synthesis of a new antineoplastic drug candidate derived from estrogen-nitrosourea, linked via click chemistry. The properties were predicted using SwissADME. ERα in complex with estrogen was obtained from the Protein Data Bank: 1ERE. The structures were prepared in AutoDockTools 1.5.7 and Avogadro 1.2.0. Molecular docking was performed with AutoDock 4.2.6 and analyzed in Discovery Studio Visualizer v24.1.0.23298. Lipinski, Ghose, Veber, and Muegge rules were satisfied, and the molecule was classified as drug-like. High oral absorption is expected. Two of the three hydrogen bonds with the same amino acid residues as estradiol, Arg-394 and His-524, were observed. The drug candidate has structural characteristics predicted to be suitable for orally active molecules and affinity for ERα.