Two new thiadiazole imidazolium salicylidene Schiff bases (TISSBs) were successfully synthesized, and their structures were analyzed comprehensively using spectroscopic techniques. The results of the MTT assay showed that TISSB2 was the safest and most effective anti-breast cancer agent. The anti-angiogenic activity of TISSB2 was evaluated using in vivo tests in Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice. The degree of angiogenesis was assessed by measuring the levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1). The results of biochemical, immunohistochemical, and histopathological examinations indicated that TISSB2 could restore the normal functional indices of the injured liver, as evident from the downregulated TGF-β1, TNF-α, and VEGF levels reverting to normal values. Moreover, in the molecular docking study, TISSB2 exhibited stronger interactions with VEGFR-2 and NF-κB proteins, with binding affinity scores of -11.79 and -9.25 kcal mol-1, respectively. These stronger interactions involved H-bonding, ionic bonds, and hydrophobic π-interactions. Overall, TISSB2 can be a promising therapeutic option for the treatment of EAC-induced tumour angiogenesis.
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