A new series of 1,3,4-thiadiazin-3-ium bromide derivatives 9a–g were prepared as a six-member ring by
interactions between 4-substituted thiosemicarbazides 8a–e and a-halo ketones 2a,b. The reaction was
conducted using hydrazine-NH2 and yielded a hexagonal shape. The structures of all obtained
compounds have been verified using IR, NMR spectra, mass spectrometry, elemental analysis, and X-ray
crystallography. The X-ray crystallographic analysis of compounds 9a and 9b has revealed that the salt is
formed with the nitrogen atom N3 when the aromatic substituents 9a and 9d are present, but in the
case of compounds 9b, 9c, 9e, 9f, and 9g with the aliphatic substituent, the salt is formed outside the
ring. Compounds 9a–g were evaluated for antiproliferative activity as multitargeted inhibitors. Results
revealed that targets 9a–g displayed good antiproliferative activity, with GI50 ranging from 38 nM to
66 nM against a panel of four cancer cell lines compared to the reference Erlotinib (GI50 = 33 nM).
Compounds 9a, 9c, and 9d were the most potent antiproliferative derivatives, with GI50 values of 43, 38,
and 47 nM, respectively. Compounds 9a, 9c, and 9d were evaluated for their inhibitory activity against
EGFR, BRAFV600E, and VEGFR-2. The in vitro experiments demonstrated that the compounds being
examined exhibit potent antiproliferative properties and have the potential to function as multitargeted
inhibitors. In addition, the western blotting investigation demonstrated the inhibitory effects of 9c on
EGFR, BRAFV600E, and VEGFR-2.