Synthesis, Cytotoxicity, Molecular Docking and ADME Assay of Novel Morpholine appended 1,2,3-Triazole Analogues

Synthesis of novel 4-(1-(2-cyclopropylphenyl)-2-(4-substituted-1H-1,2,3-triazol-1-yl)ethyl)morpholine analogues were demonstrated by conventional synthetic procedures. The structure of all the newly synthesized compounds were determined by H-1-NMR, C-13-NMR, HRMS and CHN analysis. Cytotoxicity of all synthesized compounds were tested against MCF-7 Cell lines in different concentrations. The IC50 value of compounds was calculated using graph Pad Prism Version5.1. 4-chloro substituted analogue exhibited superior result than the standard reference Doxorubicin drug. Compounds which are containing 3-methoxy, 2-methoxy and 4-methoxy substituents showed a moderate effect, and 2-chloro, 3-triflouromethyl and 2-methyl substituted analogues showed lower results. Molecular docking studies performed on the crystal structure of human estrogen receptor alpha ligand-binding domain with all molecules and are well in agreement with cell line studies. The predicted pharmacokinetics support that these compounds have more drug-likeness properties.