Design, synthesis and structure-activity relationship of novel semi-synthetic flavonoids as antiproliferative agents

4^th International Conference on Medicinal Chemistry & Computer Aided Drug Designing

November 02-04, 2015 Atlanta, USA

Reem K Arafa1,4, Fatma A Ragab 1, Tawfik A A Yahya2 and Mona M El-Naa3

1Cairo University, Egypt 2Sana�a University, Yemen 3October University for Modern Sciences and Arts, Egypt 4Zewail City of Science and Technology, Egypt

Posters-Accepted Abstracts: Med chem

Abstract :

Naturally occuring flavonoids have elicited a proven role as capacity having agents for the management of cancer. Thus, this research deals with the design and synthesis of semisynthetic flavonoid scaffold based derivatives viz., furochalcones (3a-e, 6a-d and 9ad), furoflavones (10a-d, 11a-d, 12a-d, 18a&b), flavones (21a-d), furoaurones (13a,b, 14a-d and 15a-d) and 7-styrylfurochromones (22a-d and 25a-e). The novel compounds were evaluated for their antiproliferative activity against a panel of 60 cancer cell lines comprising 9 types of tumors. Ten compounds belonging to the major subgroups of flavonoids viz., furochalcones (3a, 3d, 6b, 9a and 9b), furoflavones (12a and 12c), furoaurones (15d), styrylfurochromones (25b and 25e) showed very promising activity. These active compounds were also evaluated in vitro as kinase inhibitors against CDK2/cyclin E1, CDK4/cyclin D1 and GSK-3�² and the best inhibition was displayed against GSK-3�² with the allylfurochalcone derivative 9b exhibiting 80% decrease in GSK-3�² catalytic activity. On the other hand, the styrylfurochromone 25e interestingly showed a 13% enhancement of GSK-3�² catalytic power and a 12% reduction in CDK4/cyclinD1 activity. Finally, the in vivo anti-tumor activity of 25e was evaluated against breast cancer induced in mice. The results showed a profound anti-tumor effect of 25e that accompanies a significant increase and decrease in the levels of GSK-3�² and cyclin D1, respectively.

Biography :

Email: rkhidr@zewailcity.edu.eg