Synthesis, Molecular Docking Screening and Anti-Proliferative Potency Evaluation of Some New Imidazo[2,1- b ]Thiazole Linked Thiadiazole Conjugates.

Background: Imidazo[2,1- b ]thiazole scaffolds were reported to possess various pharmaceutical activities.
Results: The novel compound named methyl-2-(1-(3-methyl-6-( p -tolyl)imidazo[2,1- b ]thiazol-2-yl)ethylidene)hydrazine-1-carbodithioate 3 acted as a predecessor molecule for the synthesis of new thiadiazole derivatives incorporating imidazo[2,1- b ]thiazole moiety. The reaction of 3 with the appropriate hydrazonoyl halide derivatives 4a - j and 7 - 9 had produced the respective 1,3,4-thiadiazole derivatives 6a - j and 10 - 12 . The chemical composition of all the newly synthesized derivatives were confirmed by their microanalytical and spectral data (FT-IR, mass spectrometry, ¹ H-NMR and ¹³ C-NMR). All the produced novel compounds were screened for their anti-proliferative efficacy on hepatic cancer cell lines (HepG ₂ ). In addition, a computational molecular docking study was carried out to determine the ability of the synthesized thiadiazole molecules to interact with active site of the target Glypican-3 protein (GPC-3). Moreover, the physiochemical properties of the synthesized compounds were derived to determine the viability of the compounds as drug candidates for hepatic cancer.
Conclusion: All the tested compounds had exhibited good anti-proliferative efficacy against hepatic cancer cell lines. In addition, the molecular docking results showed strong binding interactions of the synthesized compounds with the target GPC-3 protein with lower energy scores. Thus, such novel compounds may act as promising candidates as drugs against hepatocellular carcinoma.