Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based Heterocycles

Abstract

A series of new morpholinylchalcones was prepared and then used as building blocks for constructing a series of 7-morpholino-2-thioxo-2,3-dihydropyrido[2,3-<i>d</i>]pyrimidin-4(1<i>H</i>)-ones via their reaction with 6-aminothiouracil. The latter thiones reacted with the appropriate hydrazonoyl chloride to give the corresponding pyrido[2,3-<i>d</i>][1,2,4]triazolo[4,3-<i>a</i>]pyrimidin-5(1<i>H</i>)-ones. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data and the mechanisms of their formation were also discussed. Most of the synthesized compounds were tested for in vitro activity against human lung cancer (A-549) and human hepatocellular carcinoma (HepG-2) cell lines compared with the employed standard antitumor drug (cisplatin) and the results revealed that compounds <b>8</b>, <b>4e</b> and <b>7b</b> have promising activities against the A-549 cell line (IC₅₀ values of 2.78 ± 0.86 μg/mL, 5.37 ± 0.95 μg/mL and 5.70 ± 0.91 μg/mL, respectively) while compound <b>7b</b> has promising activity against the HepG-2 cell lines (IC₅₀ = 3.54 ± 1.11 μg/mL). Moreover, computational studies using MOE 2014.09 software supported the biological activity results.