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.
- 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt. Electronic address: [email protected].
- 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: [email protected].
- 8. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Abbassia, P.O. Box 11566, Egypt.
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).