Design, synthesis, anticancer activity and docking studies of theophylline containing 1,2,3-triazoles with variant amide derivatives

Abstract

A new series of theophylline analogues containing 1,2,3-triazoles with different amide groups (<b>22-41</b>) has been designed and synthesized, and their biological activities have been evaluated as potential anticancer agents. The anticancer activities of the synthesized compounds were studied in four cancer cell lines <i>viz.</i> lung (A549), colon (HT-29), breast (MCF-7) and melanoma (A375). Furthermore, these compounds were screened for computational ADME and Lipinski's analysis followed by molecular docking and binding energy calculations against the various therapeutic targets involved in cell proliferation. The <i>in vitro</i> results demonstrate that compounds <b>22</b>, <b>27</b>, <b>36</b> and <b>40</b> have pivotal anticancer activity. Among these, compounds <b>22</b> and <b>27</b> have significant cytotoxic activity in all three cell lines; the <i>in silico</i> docking studies also reveal that compounds <b>22</b>, <b>27</b> and <b>36</b> have good dock scores, binding affinities and binding energies towards human epidermal growth factor receptor 2. This is the first report to demonstrate theophylline hybrids containing 1,2,3-triazoles as potential anticancer agents.