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 H-1 NMR, C-13 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 mu M, 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 mu M. 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.

Automated summary

A series of novel tetrahydro-2H-1,3,5-thiadiazine-2-thiones compounds were synthesized and characterized. The compounds showed promising anticancer activity against HeLa cell line, especially compounds 3, 5, 6, and 9 with IC50 values <4 μM. The compounds also exhibited potent anti-inflammatory potential by inhibiting nitric oxide (NO). Docking studies revealed strong interactions between the compounds and inducible NO synthase enzyme, supporting the in vitro results. These compounds could serve as potential candidates for the development of anticancer drugs.