Biphenyl sulfonylurea Analogs as novel antiangiogenic agents: A repositioning and molecular modelling strategy

The therapeutic value of blocking VEGFR-2 in cancer treatment has been established. Antidiabetic sulfonylurea-linked biphenyl compounds have been designed, synthesized, and screened as anticancer agents by a repositioning approach. All synthesized compounds were screened for anti-proliferative activities against breast tumour cells namely MCF-7 and MDA-MB-231 using MTT assay, from the series of compounds 9c and 10a showed IC₅₀ values of 29.6, 27.8, and 28.7, 32.3 μM compared to sorafenib. Further studies revealed the ability of 9c and 10a to induce apoptosis via caspase-3 activation. The most active cytotoxic compound 9c was further assessed employing the CAM assay and % VEGFR expression assay, and results showed a considerable anti-angiogenic effect. Molecular docking and molecular dynamics simulation along with ADMET predictions were also studied. Finally, acute oral toxicity results depicted that 9c and 10a could be categorized as category of five drugs. Scrutinizing the obtained results revealed that, when applied to in silico and experimental tests as a possible anti-angiogenic agent, the developed compounds demonstrated an acceptable anticancer profile.