Synthesis, Anticancer Evaluation, and Molecular Docking Studies of Novel (4-Hydroxy-2-Thioxo-3,4-Dihydro-2H-[1,3]Thiazin-6-Yl)-Chromen-2-Ones via a Multicomponent Approach

A series of coumarin-substituted 1,3-thiazine-2-thione derivatives (4a-m) were synthesized via the multicomponent reaction of 3-chloro-3-(2-oxo-2H-chromen-3-yl)acrylaldehyde (1) carbon disulfide (2), and various primary amines (3), in presence of triethylamine and acetonitrile under stirring with good yields. The structures of all the synthesized compounds were characterized by analytical and spectral studies. Further, the synthesized compounds were screened for their in vitro antiproliferative activities against different cancer cell lines (A549, MDA-MB-231, MCF7, HeLa, and B16F10). Studies on the molecular interactions to recognize the hypothetical binding motif of the title compounds with the target Hsp 100 were carried out employing the Schrodinger software. Compounds 4a, 4c and 4m showed activity against all the five cell lines compared with the reference drug, and 4a exhibited the least IC50 concentration of 7.56 +/- 1.07g/mL against MCF7. This in vitro anticancer result was supported by in silico docking and in silico ADME (absorption, distribution, metabolism, and excretion) studies as well.