Synthesis, characterization, anticancer, anti-inflammatory activities, and docking studies of 3,5-disubstituted thiadiazine-2-thiones

In the search for potent bioactive compounds, a series of tetrahydro-2H-1,3,5-thiadiazine-2-thiones (1–13) were synthesized in good yield and characterized by means of 1H NMR, 13C NMR, and mass spectral data. The anticancer activity of the compounds was evaluated against HeLa cell line and anti-inflammatory potential via nitric oxide (NO) inhibition. Among the screened compounds, 2-(5-(3-methoxypropyl)-6-thioxo-1,3,5-thiadiazinan-3-yl) propionic acid (3), 2-(5-cyclopropyl-6-thioxo-1,3,5-thiadiazinan-3-yl) propionic acid (5), 2-(5-cyclopropyl)-6-thioxo-1,3,5-thiadiazinan-3-yl) acetic acid (6), and 2-(5-butyl-6-thioxo-1,3,5-thiadiazinan-3-yl) acetic acid (9) were the most potent against HeLa cell line with IC50 values <4 µM, whereas the rest of the series exhibited moderate-to-good activities. All the compounds were potent NO inhibitors with IC50 values ranging from <0.4 to 14.9 µM. Docking studies, binding orientations, and interaction plots showed strong interaction of the studied compounds with the inducible NO synthase enzyme via strong hydrogen bonds and hydrophobic interactions, which authenticate the in vitro results. These newly synthesized compounds could lead to the discovery of anticancer drugs.