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Design, synthesis, and anticancer evaluation of N-sulfonylpiperidines as potential VEGFR-2 inhibitors, apoptotic inducers.
Elgammal, Walid E; Halawa, Ahmed H; Eissa, Ibrahim H; Elkady, Hazem; Metwaly, Ahmed M; Hassan, Saber M; El-Agrody, Ahmed M.
Afiliación
  • Elgammal WE; Department of Chemistry, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt. Electronic address: walidebaied.sci85@azhar.edu.eg.
  • Halawa AH; Department of Chemistry, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt.
  • Eissa IH; Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.
  • Elkady H; Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.
  • Metwaly AM; Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt; Biopharmaceutical Products Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexan
  • Hassan SM; Department of Chemistry, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt.
  • El-Agrody AM; Department of Chemistry, Faculty of Science, Al-Azhar University, Nasr City, Cairo, Egypt.
Bioorg Chem ; 145: 107157, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38340473
ABSTRACT
A new panel of N-sulfonylpiperidine derivatives has been designed and synthesized as vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors. Anti-proliferative activities of the synthesized members were tested against colorectal carcinoma (HCT-116), hepatocellular carcinoma (HepG-2), and breast cancer (MCF-7) cell lines. Compounds 3a, 4, 8, and 9 showed the highest activities against the tested cell lines. In particular, compound 8 showed excellent activities against HCT-116, HepG-2, and MCF-7 with IC50 values of 3.94, 3.76, and 4.43 µM, respectively. Such IC50 values are comparable to vinblastine (IC50 = 3.21, 7.35, 5.83 µM, respectively) and doxorubicin (IC50 = 6.74, 7.52, 8.19 µM, respectively). In vitro VEGFR-2 inhibitory activity of the most promising molecules (3a, 4, 8, and 9) indicated that compound 8 is the highest VEGFR-2 inhibitor with an IC50 of 0.0554 µM, compared to sorafenib (IC50 = 0.0416 µM). The most promising candidates (3a, 4, 8, and 9) were subjected to flow cytometry analyses to assess their effects on the cell cycle behavior and the apoptotic power against the three tested cell lines (HCT-116, HepG-2, and MCF-7). The tested compound arrested the tumor cells at both the G2/M and Pre-G1 phases. In addition, compound 9 was proved as the most effective apoptotic inducer among the tested compounds against the tested cells. Molecular docking studies against VEGFR-2 (PDB ID 2OH4) revealed good binding modes of the synthesized compound similar to that of sorafenib. Computational investigation of ADMET parameters revealed the drug-likeness of the synthesized compounds.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Hepáticas / Antineoplásicos Límite: Humans Idioma: En Revista: Bioorg Chem Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Hepáticas / Antineoplásicos Límite: Humans Idioma: En Revista: Bioorg Chem Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos