Synthesis and Molecular Docking of Some Novel 3-Thiazolyl-Coumarins as Inhibitors of VEGFR-2 Kinase

One crucial strategy for the treatment of breast cancer involves focusing on the Vascular Endothelial Growth Factor Receptor (VEGFR-2) signaling system. Consequently, the development of new (VEGFR-2) inhibitors is of the utmost importance. In this study, novel 3-thiazolhydrazinylcoumarins were designed and synthesized via the reaction of phenylazoacetylcoumarin with various hydrazonoyl halides and alpha-bromoketones. By using elemental and spectral analysis data (IR, H-1-NMR, C-13-NMR, and Mass), the ascribed structures for all newly synthesized compounds were clarified, and the mechanisms underlying their formation were delineated. The molecular docking studies of the resulting 6-(phenyldiazenyl)-2H-chromen-2-one (3, 6a-e, 10a-c and 12a-c) derivatives were assessed against VEGFR-2 and demonstrated comparable activities to that of Sorafenib (approved medicine) with compounds 6d and 6b showing the highest binding scores (-9.900 and -9.819 kcal/mol, respectively). The cytotoxicity of the most active thiazole derivatives 6d, 6b, 6c, 10c and 10a were investigated for their human breast cancer (MCF-7) cell line and normal cell line LLC-Mk2 using MTT assay and Sorafenib as the reference drug. The results revealed that compounds 6d and 6b exhibited greater anticancer activities (IC50 = 10.5 +/- 0.71 and 11.2 +/- 0.80 mu M, respectively) than the Sorafenib reference drug (IC50 = 5.10 +/- 0.49 mu M). Therefore, the present study demonstrated that thiazolyl coumarins are potential (VEGFR-2) inhibitors and pave the way for the synthesis of additional libraries based on the reported scaffold, which could eventually lead to the development of efficient treatment for breast cancer.

Automated summary

One crucial strategy for the treatment of breast cancer involves targeting the VEGFR-2 signaling system. In this study, new 3-thiazolhydrazinylcoumarins were synthesized and assessed for their inhibitory activity against VEGFR-2. The most active compounds exhibited comparable activities to the approved medicine Sorafenib and demonstrated greater anticancer activities than Sorafenib in breast cancer cell lines.