Exploration of Heterocyclic Molecules Inhibiting Angiogenesis via VEGF Pathway Targeting VEGFR-2: An In Silico Approach

• Published in: Proceedings of the National Academy of Sciences, India. Section B: Biological sciences India. Section B: Biological sciences, 2024-02, Vol.94 (1), p.75-86
• Main Authors: Nippu, B. N., Kumaraswamy, H. M., Satyanarayan, N. D.
• Format: Article
• Language: English
• Subjects: algorithms; Amino acids; Angiogenesis; antineoplastic agents; Behavioral Sciences; Biomedical and Life Sciences; Cancer; Cancer therapies; cancer therapy; computer simulation; Drug discovery; India; Life Sciences; Ligands; Medical prognosis; Nucleic Acid Chemistry; Pharmaceutical industry; Plant Biochemistry; prognosis; quinoline; Research Article; Signal transduction; tyrosine; Vascular endothelial growth factor; vascular endothelial growth factor receptor-2; Vascular endothelial growth factor receptors
• ISSN: 0369-8211; 2250-1746
• DOI: 10.1007/s40011-023-01501-3

Cancer drug discovery is expensive, time-consuming, and hits the economy of any pharmaceutical industry. To minimize the time, a rational approach needs to be adopted. In silico drug discovery is the most convenient approach in the process of identifying the lead molecules for cancer treatment. Various signalling pathways are involved in cancer prognosis through angiogenesis. VEGFR-2 tyrosine kinase plays a pivotal role and it is a vital factor in angiogenesis. Hence, new entities that target VEGFR-2 signalling pathways are urgently needed. Based on the potent biological features of quinoline, tetrazole, and benzosulphonyl heterocyclic entities, sixteen novel compounds were designed to accomplish the purpose via an in silico ADMET and molecular docking study. The docking approaches are carried out using the Autodock Vina algorithm and BIOVIA DS 2020. The in silico ADMET results of the designed ligands showed acceptable druglikeness and ADMET values. The binding affinity among the 16 designed, SQT (10) and (11) showed a − 12.1 and − 12.0 kcal/Mol, which is higher than the standard drugs axitinib and sunitinib and binds with key amino acid residues in the active pocket such as LYS868, GLU885, ASN923, CYS919, and ASP1046. The obtained results suggest that the designed ligands may act as novel type-1 VEGFR inhibitors and encourage the synthesis and evaluation of their biological potential through in vitro and in vivo studies.