Design, synthesis, and in silico studies of novel di-(2-aryl hydrozonopropanal) arene derivatives as potent anticancer for targeting A2AR and LRP6 in HCT116 cell

This study aimed to design and synthesize novel anticancer drug candidates and then examine their anticancer activity against human cancer cell lines. The anti-proliferation of human colon cancer cells (HCT116) was examined using the MMT assay and compared to the activity of doxorubicin as chemotherapy after characterizing novel derivatives of di (2-aryl hydrazonopropane) arene by elemental analyzer, FTIR, 1H, 13C NMR, and ESI-MS. Chemoinformatic tools predicted their targets, and then molecular docking was performed to predict the binding affinity of compounds to the main receptors expressed in colon cancer: the adenosine receptor (A2AR) and the low-density lipoprotein receptor-related protein (LRP6). To form the corresponding diaryl hydrazone coupling products from the di-(2-aryl hydrazonopropane) arene derivatives, equivalent amounts of enaminones were coupled with diazotized aniline derivatives. Compound11b, containing a benzonitrile moiety, was the most potent against HCT116 cells (IC50 of 0.098  ± 0.03 μM) and had a greater binding affinity to both A2AR and LRP6 of −12.43 and −16.45 kcal/mol, respectively. Our results demonstrated that the dibenzonitrile moiety is a good part of compounds that are candidates as anticancer drugs against HCT116 cells.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research