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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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).

Related collections

Author and article information

Journal

Journal ID (iso-abbrev): Eur J Med Chem

Title: European journal of medicinal chemistry

ISSN (Electronic): 1768-3254

ISSN (Print): 0223-5234

Publication date (Electronic): Jul 15 2015

Volume: 100

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.

Article

Publisher Item ID: S0223-5234(15)30067-2

DOI: 10.1016/j.ejmech.2015.05.040

PubMed ID: 26071861

SO-VID: 8b48f3f2-e8b9-4fcf-8e1a-ae7c6133cb88

History

Keywords: Design,Docking,HepG2,Urea,VEGFR-2

Data availability:

Keywords: Design, Docking, HepG2, Urea, VEGFR-2

Comments

Comment on this article

scite_

Cited by 21

See all cited by

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

Read this article at