Nadigar Siddaram, Gattu Rohith, Ramesh Sanjay, Dharmappa Rekha N, Nanjundaswamy Vijendra Kumar, Ramesh Suhas
Postgraduate Department of Chemistry, JSS College of Arts, Commerce & Science (a recognized Research Centre of University of Mysore), Ooty Road, Mysuru-25, Karnataka, India.
Postgraduate Department of Biotechnology, JSS College of Arts, Commerce & Science (a recognized Research Centre of University of Mysore), Ooty Road, Mysuru-25, Karnataka, India.
Future Med Chem. 2024;16(21):2285-2300. doi: 10.1080/17568919.2024.2394020. Epub 2024 Sep 12.
Angiogenesis is the hallmark of cancer progression driven by VEGF/VEGFR-2 signalling pathway, inhibition of which could be a solution to tackle the progression of tumour cells and thus arresting their growth. A novel class of pyrazoles was synthesized using arginine and dibromo ketones. Antiangiogenic activity was performed by yolk sac method. Antioxidant activity was evaluated by hydroxyl and superoxide radical scavenging assays. Docking studies were performed to determine the pyrazoles' binding potential with VEGFR-2 receptor and VEGF tyrosine kinase. ADMET properties were calculated using SwissADME and admetSAR for drug-likeness. Compounds showed significant antiangiogenic effects. Compound exhibited effective hydroxyl and superoxide radical scavenging activities. Docking results confirmed the potential binding efficiency with VEGFR-2 receptor over VEGF tyrosine kinase, thus, functioning as competitive-inhibitors. ADMET studies revealed that the compounds possess favourable drug-like qualities. This study presents a novel class of pyrazoles as promising antioxidant and antiangiogenic agents with favourable drug-likeness properties.
血管生成是由血管内皮生长因子/血管内皮生长因子受体-2(VEGF/VEGFR-2)信号通路驱动的癌症进展的标志,抑制该通路可能是解决肿瘤细胞进展从而阻止其生长的一种方法。使用精氨酸和二溴酮合成了一类新型吡唑。通过卵黄囊法进行抗血管生成活性研究。通过羟基和超氧阴离子自由基清除试验评估抗氧化活性。进行对接研究以确定吡唑与VEGFR-2受体和VEGF酪氨酸激酶的结合潜力。使用SwissADME和admetSAR计算药物代谢动力学(ADMET)性质以评估药物相似性。化合物显示出显著的抗血管生成作用。化合物表现出有效的羟基和超氧阴离子自由基清除活性。对接结果证实了与VEGFR-2受体相比,与VEGF酪氨酸激酶具有更高的潜在结合效率,因此可作为竞争性抑制剂发挥作用。ADMET研究表明这些化合物具有良好的类药物性质。本研究提出了一类新型吡唑作为具有良好类药物性质的有前景的抗氧化剂和抗血管生成剂。