benzimidazole-linked-1,3,4-thiadiazol-2-amine derivatives: computational screening, synthesis, and biological evaluation as potential vegfr-2 inhibitors

Vegfr-2 expression and its activation are upregulated, causing angiogenesis. this process is significant and critical for tumor development, progression, and metastasis. as a consequence, vegfr-2 has become the center of attention for cancer treatment scientists because the inhibition of vegfr-2 kinases has become essential in the field of oncological research with the ultimate goal of stopping angiogenesis and terminating the development of malignant tumors. in this study, the target molecule inhibitors were developed via the synthesis of benzimidazole-1,3,4-thiadiazol-2-amine derivatives. out of 30 screened molecules, ap3, ap5, ap10, ap12, ap16, ap17, ap18, ap20, ap24, and ap29 which possess most drug-likeness properties are considered as the most potent and either selected for wet lab synthesis. vegfr-2 kinase assay was performed at a test concentration of 10 μm. compounds ap17 and ap29 are at top of the list due to their excellent inhibition activities of the vegfr2 kinase (ic50 values are 1.86 µm and 3.84 µm, respectively), and compared to pazopanib (the ic50 value is 0.092 µm), they displayed this activity quite well. the activity of the synthesized compounds were determined in 5 cancerous cell lines (breast-mcf-7, mda-mb-231, kidney-hek-293, and lung-a549) with sulforhodamine b (srb) assay. based on the trial, the compound ap17 displayed the best potency against a-549 with a gi50 value of 5.35 μm, more so than against hek-293 and mcf-7 cells with a gi50 value of 7.20 and 8.90 μm, respectively. the fact that only this particular compound demonstrated medium cytotoxicity against the mda-mb-231 (gi50 =18.89 μm) reflects the popularity and preference of this compound. as a consequence of the current examination, we have concluded that the inhibitors possess good potential of vegfr2 kinase for future use.