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.
Shankar
Ravi
R
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226 001, UP, India.
Chakravarti
Bandana
B
Singh
Uma Sharan
US
Ansari
Mohd Imran
MI
Deshpande
Shreekant
S
Dwivedi
Shailendra Kumar Dhar
SK
Bid
Hemant Kumar
HK
Konwar
Rituraj
R
Kharkwal
Geetika
G
Chandra
Vishal
V
Dwivedi
Anila
A
Hajela
K
K
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