作为靶向VEGFR-2的抗增殖剂的苯并恶唑连接的吡唑杂化物的设计、合成与评价
Design, Synthesis, and Evaluation of Benzoxazole-linked Pyrazole Hybrids as VEGFR-2-targeted Antiproliferative Agents.
作者信息
Deniz Elif, Çöven Furkan Ozan, Ergüç Ali, Karakuş Fuat, Kuzu Burak
机构信息
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Van Yuzuncu Yil University, Van, Türkiye.
Department of Bioengineering, Faculty of Engineering and Natural Sciences, Manisa Celal Bayar University, Manisa, Türkiye.
出版信息
Cell Biochem Biophys. 2025 Jul 2. doi: 10.1007/s12013-025-01817-z.
In this study, a series of benzoxazole-linked pyrazole compounds (20a-t) were synthesized and tested for their antiproliferative activity. Their effects on lung cancer (A549) and normal lung (CCD-34Lu) cell lines were evaluated using the MTT assay. Among them, compounds 20m and o showed strong antiproliferative effects, with IC values of 7.64 and 15.82 µM, respectively, and selectivity indices of 2.84 and 1.95 in favor of cancer cells. ELISA tests demonstrated that both compounds statistically significantly reduced VEGFR-2 protein levels by 24.8 and 28.7% at their respective IC values, indicating potential antiangiogenic properties. Molecular docking studies supported these findings by showing favorable binding of 20m and o to the VEGFR-2 receptor, with binding energies of -7.33 kcal/mol and -7.22 kcal/mol, respectively. Overall, compounds 20m and o stand out as promising candidates for further development as anticancer drugs.
在本研究中，合成了一系列苯并恶唑连接的吡唑化合物（20a - t），并测试了它们的抗增殖活性。使用MTT法评估了它们对肺癌（A549）和正常肺（CCD - 34Lu）细胞系的影响。其中，化合物20m和o表现出较强的抗增殖作用，IC值分别为7.64和15.82 μM，有利于癌细胞的选择性指数分别为2.84和1.95。ELISA测试表明，两种化合物在各自的IC值下均能使VEGFR - 2蛋白水平在统计学上显著降低24.8%和28.7%，表明具有潜在的抗血管生成特性。分子对接研究支持了这些发现，显示20m和o与VEGFR - 2受体具有良好的结合，结合能分别为-7.33 kcal/mol和-7.22 kcal/mol。总体而言，化合物20m和o作为抗癌药物进一步开发的有前景的候选物脱颖而出。
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