Novel 2-indolinone thiazole hybrids were designed and synthesized as VEGFR-2 inhibitors based on sunitinib, an FDA-approved anticancer drug. The proposed structures of the prepared 2-indolinone thiazole hybrids were confirmed based on their spectral data and CHN analyses. The target compounds were screened in vitro for their anti-VEGFR-2 activity. All tested compounds exhibited a potent submicromolar inhibition of VEGFR-2 kinase with IC₅₀ values ranging from 0.067 to 0.422 μM, relative to sunitinib reference drug (IC₅₀ = 0.075 ± 0.002 μM). Compounds 5, 15a, 15b, 17, 19c displayed excellent VEGFR-2 inhibitory activity, comparable or nearly equipotent to sunitinib. Compound 13b stood out as the most potent against VEGFR-2 showing IC₅₀ value of 0.067 ± 0.002 μM, lower than that of sunitinib. In addition, the most potent derivatives were assessed for their anticancer activity against two renal cancer cell lines. Compound 13b (IC₅₀ = 3.9 ± 0.13 μM) was more potent than sunitinib (IC₅₀ = 4.93 ± 0.16 μM) against CAKI-1 cell line. Moreover, thiazole 15b displayed excellent anticancer activity against CAKI-1 cell line (IC₅₀ = 3.31 ± 0.11 μM), superior to that of sunitinib (IC₅₀ = 4.93 ± 0.16 μM). Thiazole 15b was also equipotent to sunitinib (IC₅₀ = 1.23 ± 0.04 μM) against A498 cell line. Besides, compound 15b revealed a safety profile much better than that of sunitinib against normal human renal cells. Furthermore, a docking study revealed a proper fitting of the most active compounds into the ATP binding site of VEGFR-2, rationalizing their potent anti-VEGFR-2 activity.

根据FDA批准的抗癌药舒尼替尼，设计并合成了新型2-吲哚酮噻唑杂合物作为VEGFR-2抑制剂。基于其光谱数据和CHN分析，确定了所制备的2-吲哚酮噻唑杂化物的拟议结构。体外筛选目标化合物的抗VEGFR-2活性。相对于舒尼替尼参考药物（IC ₅₀  = 0.075±0.002μM），所有测试的化合物均表现出对VEGFR-2激酶的有效的亚微摩尔抑制作用，IC ₅₀值为0.067至0.422μM 。化合物5、15a，15b，17、19c显示出优异的VEGFR-2抑制活性，与舒尼替尼相当或几乎等效。化合物13b在对抗VEGFR-2方面表现最强，IC ₅₀值为0.067±0.002μM，低于舒尼替尼。另外，评估了最有效的衍生物对两种肾癌细胞系的抗癌活性。 对于CAKI-1细胞系，化合物13b（IC ₅₀  = 3.9± 0.13μM）比舒尼替尼（IC ₅₀ = 4.93±0.16μM ）更有效。此外，噻唑15b对CAKI-1细胞系具有出色的抗癌活性（IC ₅₀  = 3.31± 0.11μM ），优于舒尼替尼（IC ₅₀  = 4.93±0.16μM）。噻唑15b也等同于舒尼替尼（IC ₅₀ = 1.23±0.04μM）。此外，化合物15b显示出比舒尼替尼对正常人肾细胞的安全性要好得多。此外，对接研究显示，活性最高的化合物可以适当地适合VEGFR-2的ATP结合位点，从而使其有效的抗VEGFR-2活性合理化。