Synthesis and Evaluation of New Brominated Azaflavones and Azaflavanone Derivatives as Cytotoxic agents against Breast Cancer Cell Line (MCF-7)

Abstract

Background: Flavonoids encompasses flavones, isoflavones, flavanones and flavanols each possessing the benzopyranone ring system as the common structural feature, were identified as potent nonsteroidal aromatase inhibitors (NSAIs). Purpose: Azaflavones which were isosteric structural scaffolds of flavonoids were also proven to be potent NSAIs. In order to develop new NSAIs as cytotoxic agents for breast cancer, we designed some 6-bromo-2-substituted azaflavanones and azaflavone derivatives. Method: Azaflavones and Azaflavonones were synthesized by a reaction of 2-amino-6-bromoacetophenone and various aromatic aldehydes to result in different chalcones (4) using Claisen-Schmidt condensation. Further cyclization of chalcones (4), led to tetrahydroquinoline-4-ones (5) using orthophosphoric acid. In the final oxidative step, the desired dihydroquinoline-4ones (6) were obtained. Results: All the synthesized compounds were characterized by using IR, 1 H NMR and ESI-MS data and were evaluated for cytotoxic activity by using MTT assay on MCF-7 cell lines. Conclusion: Compounds with furoyl and pyridyl groups as substituents were found to be potent.

A review of the syntheses of flavanones, thioflavanones, and azaflavanones from 2'‐substituted chalcones

“…49 Furthermore, reaction between 2'-amino-5-bromochalcones and H 3 PO 4 in glacial acetic acid for 20 min at reflux also afforded 6-bromoazaflavanones in 68%-82% yields, and some of these showed good cytotoxic activity against MCF-7 cell lines. 50 2'-(N-Acetylamino)chalcones were also used for the preparation of azaflavanones. 51 For example, treatment of 2'-(N-acetylamino)chalcones (62) with 5% HCl in CH 3 OH for 6 h at reflux produced the corresponding 2'-aminochalcones by deprotection of the acetylated amine, and these intermediates underwent simultaneous 1,4addition to give azaflavanones (63) (Scheme 27).…”