Development of Isatin‐Based Schiff Bases Targeting VEGFR‐2 Inhibition: Synthesis, Characterization, Antiproliferative Properties, and QSAR Studies

• Published in: ChemMedChem 2022-07, Vol.17 (13), p.e202200164-n/a
• Main Authors: Seliem, Israa A., Panda, Siva S., Girgis, Adel S., Tran, Queen L., Said, Mona F., Bekheit, Mohamed S., Abdelnaser, Anwar, Nasr, Soad, Fayad, Walid, Soliman, Ahmed A. F., Sakhuja, Rajeev, Ibrahim, Tarek S., Abdel‐Samii, Zakaria K. M., Al‐Mahmoudy, Amany M. M.
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Angiogenesis; Antiproliferation; Antiproliferatives; Breast cancer; Cell cycle; Chemical synthesis; Colon; Colon cancer; Flow cytometry; Hybridization; Imines; Indoles; Pancreatic cancer; QSAR studies; Schiff base; Structure-activity relationships; Tumor cell lines; Vascular endothelial growth factor receptors; VEGFR2
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.202200164

Three sets of isatin‐based Schiff bases were synthesized utilizing the molecular hybridization approach. Some of the synthesized Schiff bases show significant to moderate antiproliferative properties against MCF7 (breast), HCT116 (colon), and PaCa2 (pancreatic) cancer cell lines with potency compared to reference drugs 5‐fluorouracil (5‐FU) and Sunitinib. Among all, compound 17 f (3‐((1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)imino)‐1‐((1‐(2‐methoxyphenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)‐5‐methylindolin‐2‐one) exhibits promising antiproliferative properties against the MCF7 cancer cell line with 2.1‐fold more potency than Sunitinib. However, among all the synthesized compounds, three (5‐methylisatin derivatives) were the most effective against HCT116 in comparison to 5‐FU. Compound 17 f exhibited the highest anti‐angiogenic effect on the vasculature as it significantly reduced BV from 43 mm to 2 mm in comparison to 5.7 mm for Sunitinib and flow cytometry supports the arrest of the cell cycle at G1/S phases. In addition, compound 17 f also showed high VEGFR‐2 inhibition properties against breast cancer cell lines. Robust 2D‐QSAR studies supported the biological data. Development of anticancer drug candidates: Design and synthesis of isatin‐based Schiff bases are reported. Some of the newly synthesized Schiff bases show potential anticancer activity against breast cancer cell lines with lower toxicity toward normal cells. Thus, these Schiff bases could lead to the development of potential drug candidates for breast cancer.