Design and synthesis of 1,4-benzothiazine derivatives with promising effects against colorectal cancer cells

Abstract

<p>In this study, we designed and synthesized a series of 1,4-benzothiazine and evaluated them for anticancer activity toward HT-29 human colon cancer cells using SRB assay. Before the synthesis, docking studies were performed using various molecular targets of colon cancer including IL-2, IL-6, COX-2, caspase-3, and caspase-8. The molecular dynamic (MD) simulation was also executed to examine the stability of ligand-receptor complex of more stable dock conformation. Further computational study was carried out in order to predict the pharmacokinetic profile of titled compounds. Among 34 tested compounds, compounds <b>AR13</b> and <b>AR15</b> were found to be active against HT-29 cells (GI₅₀ < 10 μM)_. Moreover, Compounds <b>AR5</b>, <b>AR22</b>, and <b>AR34</b> showed the moderate activity with GI₅₀ < 70 μM. The binding energy was found to be > −5 kcal/mol for <b>AR13</b> and <b>AR15</b> with all the molecular targets and the ligand-protein complex was found stable after its formation. Again, computational analysis revealed that both molecules <b>AR13</b> and <b>AR15</b> had good ADMET profiling. These encouraging outcomes allowed us to conclude that both <b>AR13</b> and <b>AR15</b> may emerge as lead compounds against colon cancer.</p