Home|Journals|Articles by Year|Audio Abstracts
 

Original Article

J App Pharm Sci. 2017; 7(2): 049-066


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.




Abstract

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.

Key words: Coumarin sulfonyl chlorides, non-cytotoxic, anti-angiogenic, molecular docking






Full-text options


Share this Article


Online Article Submission
• ejmanager.com




ejPort - eJManager.com
Refer & Earn
JournalList
About BiblioMed
License Information
Terms & Conditions
Privacy Policy
Contact Us

The articles in Bibliomed are open access articles licensed under Creative Commons Attribution 4.0 International License (CC BY), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.