Synthesis and biological evaluation of 3,4,6-triaryl-2-pyranones as a potential new class of anti-breast cancer agents.
A series of 3,4,6-triaryl-2-pyranones, new class of anti-breast cancer agents, have been synthesized as a structural variants of cyclic triphenylethylenes by replacing the fused benzene ring with pendant phenyl ring to mimic the phenolic A ring of estradiol. Nine of these newly synthesized pyranones exhibited significant anti-proliferative activity in both ER+ve and ER-ve breast cancer cell lines. Four active non-cytotoxic compounds 5c, 5d, 5g and 5h showed specific and selective cytotoxicity and two compounds 5d and 5h induced significant DNA fragmentation in both MCF-7 and MDA-MB-231 cell lines. Based on RBA studies, the molecules probably act in an ER-independent mechanism. The involved pathway was observed as caspase-dependant apoptosis in MCF-7 cells. However, the particular caspases involved and the possible cellular target through which this series of compounds mediate cell death are not known.
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226 001, UP, India.
Ravi
R
Shankar
Bandana
B
Chakravarti
Uma Sharan
US
Singh
Mohd Imran
MI
Ansari
Shreekant
S
Deshpande
Shailendra Kumar Dhar
SK
Dwivedi
Hemant Kumar
HK
Bid
Rituraj
R
Konwar
Geetika
G
Kharkwal
Vishal
V
Chandra
Anila
A
Dwivedi
K
K
Hajela
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry; D011753:Pyrones / Q000737:chemistry* / Q000494:pharmacology*; D011759:Pyrrolidines / Q000737:chemistry
D000970:Antineoplastic Agents; D010880:Piperidines; D011753:Pyrones; D011759:Pyrrolidines; C032519:pyrrolidine