2. Academic Validation
  3. Indoline ureas as potential anti-hepatocellular carcinoma agents targeting VEGFR-2: Synthesis, in vitro biological evaluation and molecular docking

Indoline ureas as potential anti-hepatocellular carcinoma agents targeting VEGFR-2: Synthesis, in vitro biological evaluation and molecular docking

  • Eur J Med Chem. 2015 Jul 15:100:89-97. doi: 10.1016/j.ejmech.2015.05.040.
Wagdy M Eldehna 1,  Mohamed Fares 2,  Hany S Ibrahim 2,  Mohamed H Aly 3,  Suher Zada 4,  Mamdouh M Ali 5,  Sahar M Abou-Seri 6,  Hatem A Abdel-Aziz 7,  Dalal A Abou El Ella 8
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt. Electronic address: wagdy2000@gmail.com.
  • 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt.
  • 3 Department of Pharmacology and Toxicology, Faculty of Pharmacy, British University in Egypt, Cairo, Egypt; Department of Biology, The American University in Cairo, P.O. Box 11835, New Cairo, Egypt.
  • 4 Department of Biology, The American University in Cairo, P.O. Box 11835, New Cairo, Egypt.
  • 5 Biochemistry Department, Division of Genetic Engineering and Biotechnology, National Research Centre, Dokki, 12622 Giza, Egypt.
  • 6 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, P.O. Box 11562, Egypt.
  • 7 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Applied Organic Chemistry, National Research Center, Dokki, Giza, P.O. Box 12622, Egypt. Electronic address: hatem_741@yahoo.com.
  • 8 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Abbassia, P.O. Box 11566, Egypt.
PMID: 26071861 DOI: 10.1016/j.ejmech.2015.05.040
Abstract

In our effort to develop potent and effective agents with anti-proliferative activity towards HepG2 hepatocellular carcinoma cells with potential inhibitory activity against VEGFR-2, a novel series of 1-(4-((2-oxoindolin-3-ylidene)amino)phenyl)-3-arylureas was designed and synthesized. All the newly prepared ureas 9a-x were evaluated in vitro for their anti-proliferative activity against HepG2 hepatocellular carcinoma cell line. Compounds 9a-c, 9e, 9f, 9j, 9m-o, 9t-v and 9x exhibited good activity against HepG2 Cancer cells (IC50 = 1.22 ± 0.11-8.37 ± 0.85 μM) comparable to that of doxorubicin and sorafinib (IC50 = 2.90 ± 0.36 and 3.40 ± 0.25 μM, respectively). These thirteen compounds were further evaluated for their inhibitory activity against VEGFR-2. Compound 9x emerged as the most active counterpart against VEGFR-2 with IC50 value of 0.31 ± 0.04 μM. Furthermore, a molecular docking of the tested compounds was carried out in order to investigate their binding pattern with the prospective target, VEGFR-2 (PDB-code: 4ASD).

Keywords

Design; Docking; HepG2; Urea; VEGFR-2.

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