4-Aryl-4H-naphthopyrans derivatives: one-pot synthesis, evaluation of Src kinase inhibitory and anti-proliferative activities.
BACKGROUND
A series of 2-amino-4-aryl-4H-benzo[h or f]chromene-3-carbonitrile derivatives were synthesized and evaluated for inhibition of Src kinase and cell proliferation in breast carcinoma (BT-20) cell lines.


METHODS
The one-pot, three-component reaction of α or β-naphthol, malonitrile and an aromatic aldehyde in the presence of diammonium hydrogen phosphate was afforded the corresponding 2-amino-4-aryl-4H-benzo[h or f]chromene-3-carbonitrile derivatives, All target compounds were evaluated for inhibition of Src kinase and cell proliferation in breast carcinoma (BT-20) cell lines.


RESULTS
Among all tested compounds, unsubstituted 4-phenyl analog 4a showed Src kinas inhibitory effect with IC50 value of 28.1 μM and was the most potent compound in this series. In general, the compounds were moderately active against BT-20. 3-Nitro-phenyl 4e and 3-pyridinyl 4h derivatives inhibited the cell proliferation of BT-20 cells by 33% and 31.5%, respectively, and found to be more potent compared to doxorubicin (25% inhibition of cell growth).


CONCLUSIONS
The data indicate that 4-aryl-4H-naphthopyrans scaffold has the potential to be optimized further for designing more potent Src kinase inhibitors and/or anticancer lead compounds.
Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. akbarzad@tums.ac.ir.
Ali
A
Rafinejad
Asal
A
Fallah-Tafti
Rakesh
R
Tiwari
Amir Nasrolahi
AN
Shirazi
Deendayal
D
Mandal
Abbas
A
Shafiee
Keykavous
K
Parang
Alireza
A
Foroumadi
Tahmineh
T
Akbarzadeh