Research Article | Volume: 7, Issue: 2, February, 2017

Synthesis and molecular docking of novel non-cytotoxic anti-angiogenic sulfonyl coumarin derivatives against hepatocellular carcinoma cells in vitro

Eslam R. El- Sawy Manal Sh Ebaid Hanaa M. Rady Aziza B. Shalby Khadiga M. Ahmed Heba M. Abo-Salem   

Open Access   

Published:  Feb 27, 2017

DOI: 10.7324/JAPS.2017.70207

Resistance to conventional cytotoxic therapeutics, emphasize the need for efforts to develop non-cytotoxic targeted molecular therapies directed against the pathways involved in the angiogenesis. In this work a new series of coumarin derivatives was synthesized starting from 2-oxo-2H-coumarin-6-sulfonyl chloride (1), 6-nitro-2-oxo-2H-coumarin-3-sulfonyl chloride (10) and 6-amino coumarin-2-one (19). The tested compounds 4, 5, 8, 12, 13 and 14 were non-cytotoxic against hepatocellular carcinoma cells (HepG2) using MMT. These non-cytotoxic compounds were evaluated as anti-angiogenic agent. Results revealed that compounds 8 and 12 exhibited MMP-independent anti-migratory activity, while compounds 4, 5, 8, 13 and 14 induced MMP-dependent anti-migratory activity against hepatocellular carcinoma. Therefore, these coumarin molecules can be utilized as lead compounds to develop potential non-toxic angiogenesis inhibitors and small molecular ligands to target (HepG2). Compound 4 considered a promising anti-angiogenic agent, where it exhibited MMP-dependent anti-migratory activity and down regulated CD105. Furthermore, the molecular docking of the tested compounds was carried out in order to investigate their binding pattern with the prospective target, MMP-2 (PDB-code: 1HOV). The docking results indicate that all tested compounds exhibited better docking score and good fitting inside the active side of MMP-2 (PDB-code: 1HOV) which was in concomitant with biological results.

Keyword:     Coumarin sulfonyl chlorides non-cytotoxic anti-angiogenic molecular docking.


El-Sawy ER, Ebaid MS, Rady HM, Shalby AB, Ahmed KM, AboSalem HM. Synthesis and molecular docking of novel noncytotoxic anti-angiogenic sulfonyl coumarin derivatives against hepatocellular carcinoma cells in vitro. J App Pharm Sci, 2017; 7 (02): 049-066.

Copyright:The Author(s). This is an open access article distributed under the Creative Commons Attribution Non-Commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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