Fluorinated 2'-hydroxychalcones as garcinol analogs with enhanced antioxidant and anticancer activities.
Chalcones are involved in the synthesis of flavonoids and are themselves known to exhibit multiple pharmacological properties. However, compared to other structurally similar phytochemicals like garcinol and curcumin, the therapeutic use of chalcones is limited because of their lower bioavailability and rapid metabolic clearance from biological system. In the present work, we have attempted to overcome these limitations in case of 2'-hydroxychalcones through bioisosteric substitution of fluoro groups in place of phenolic hydroxyls. The fluorinated chalcones were found to be more potent antioxidant and anti-proliferative compounds than their hydroxyl counterparts indicating the influence of metabolically stable C-F bonds towards bioavailability. The difluoro derivatives were found to be most effective against human pancreatic BxPC-3 cancer cells which possess up-regulated COX-2 expression and also showed activity against human breast cancer BT-20 cells with triple negative phenotype, suggesting that these compounds will have broader application in the future.
Padhye
Subhash
S
Department of Pathology, Barbara Ann Karmanos Cancer Center and Wayne State University School of Medicine, Detroit, MI 48201, USA.
Ahmad
Aamir
A
Oswal
Nikhil
N
Dandawate
Prasad
P
Rub
Rukhsana A
RA
Deshpande
Jyoti
J
Swamy
K Venkateswara
KV
Sarkar
Fazlul H
FH
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D047188:Chalcones / Q000737:chemistry*; D003198:Computer Simulation; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D054879:Halogenation; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D017434:Protein Structure, Tertiary; D013482:Superoxide Dismutase / Q000378:metabolism; D013729:Terpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D000975:Antioxidants; D047188:Chalcones; D013729:Terpenes; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D013482:Superoxide Dismutase; C054597:garcinol; C013031:2'-hydroxychalcone