In silico study of four new phenoxybenzoic acid - isatin derivatives: targeting VEGFR and cancer
DOI:
https://doi.org/10.60988/p.v37i2S.216Keywords:
in silico; cancer; isatin derivatives; phenoxybenzoic acid; VEGFRAbstract
Cancer remains a major global health challenge, necessitating the development of novel therapeutic agents. This study hypothesizes that phenoxybenzoic acid derivatives can effectively inhibit the vascular endothelial growth factor receptor (VEGFR; Protein Data Bank code: 4ASE); a key molecular target in cancer therapy. Four compounds – designated F1, F2, F3, and F4 – were designed and synthesized to test this hypothesis. Their molecular structures were sketched using ChemDraw Ultra version 12.0, and their binding affinities were evaluated through molecular docking simulations conducted with the Molecular Operating Environment (MOE) program. Docking scores and root-mean-square deviation values were analysed in order to assess the compounds’ potential effectiveness. Compared to sorafenib, a clinically approved VEGFR inhibitor, the synthesized compounds exhibited significant binding affinities within the receptor’s active site, supporting their potential as anticancer agents. These findings provide a rationale for further biological evaluation and optimization of these compounds for targeted cancer therapy.
References
1. Alibeg A.A.A., Mohammed M.H. Design, synthesis, in silico study and biological evaluation of new isatin-sulfonamide derivatives by using mono amide linker as possible as histone deacetylase inhibitors. Pol. Merkur. Lekarski 52(2), 178–188, 2024. DOI: 10.36740/Merkur202402106
2. Alibeg A.A.A., Mohammed M.H. Molecular docking, synthesis, characteristics and preliminary cytotoxic study of new coumarin-sulfonamide derivatives as histone deacetylase inhibitors. Wiad. Lek. 77(3), 514–525, 2024. DOI: 10.36740/WLek202403118
3. Alanazi M.M., Alanazi A.S. Novel 7-deazapurine incorporating isatin hybrid compounds as protein kinase inhibitors: design, synthesis, in silico studies, and antiproliferative evaluation. Molecules 28(15), 5869, 2023. DOI: 10.3390/molecules28155869
4. Yousef R.G., Eldehna W.M., Elwan A., Abdelaziz A.S., Mehany A.B.M., Gobaara I.M.M., et al. Design, synthesis, in silico and in vitro studies of new immunomodulatory anticancer nicotinamide derivatives targeting VEGFR-2. Molecules 27(13), 4079, 2022. DOI: 10.3390/molecules27134079
5. Ghalehbandi S., Yuzugulen J., Pranjol M.Z.I., Pourgholami M.H. The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF. Eur. J. Pharmacol. 949, 175586, 2023. DOI: 10.1016/j.ejphar.2023.175586
6. Abdulsada A.H., Alibeg A.A.A., Wannas A.N. Synthesis and biological evaluation of some newly synthesized Schiff base derived quinazoline and cinnamaldehyde. J. Pharm. Negat. Results 13(3), 151–154, 2022. DOI: 10.47750/pnr.2022.13.03.024
7. Lopes-Coelho F., Martins F., Pereira S.A., Serpa J. Anti-angiogenic therapy: current challenges and future perspectives. Int. J. Mol. Sci. 22(7), 3765, 2021. DOI: 10.3390/ijms22073765
8. Zhong L., Li Y., Xiong L., Wang W., Wu M., Yuan T., et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct. Target. Ther. 6(1), 201, 2021. DOI: 10.1038/s41392-021-00572-w
9. Heriz M.H., Razzak Mahmood A.A., Tahtamouni L.H., Al-Sakhen M.F., Kanaan S.I., Saleh K.M., et al. New carbothioamide and carboxamide derivatives of 3-phenoxybenzoic acid as potent VEGFR-2 inhibitors: synthesis, molecular docking, and cytotoxicity assessment. Curr. Cancer Drug Targets 25(4), 412–430, 2025. DOI: 10.2174/0115680096307334240429050730
10. Naji Z.F., Naser N.H. In silico study of five new sulfonamide derivatives bearing a thiazolidine-4-one moiety: targeting carbonic anhydrase IX. Rev. Clin. Pharmacol. Pharmacokinet. Int. Ed. 38(2), 161–173, 2024. DOI: 10.61873/DAQO3640
