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

Israa A. Seliem, Siva S. Panda, Adel S. Girgis, Queen L. Tran, Mona F. Said, Mohamed S. Bekheit, Anwar Abdelnaser, Soad Nasr, Walid Fayad, Ahmed A.F. Soliman, Rajeev Sakhuja, Tarek S. Ibrahim, Zakaria K.M. Abdel-Samii, Amany M.M. Al-Mahmoudy

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere202200164
JournalChemMedChem
Volume17
Issue number13
DOIs
StatePublished - Jul 5 2022

Keywords

  • Antiproliferation
  • Indoles
  • QSAR studies
  • Schiff base
  • VEGFR2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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