TY - JOUR
T1 - Bis-chalcone analogues as potent NO production inhibitors and as cytotoxic agents
AU - Vijaya Bhaskar Reddy, M.
AU - Shen, Yuh Chiang
AU - Ohkoshi, Emika
AU - Bastow, Kenneth F.
AU - Qian, Keduo
AU - Lee, Kuo Hsiung
AU - Wu, Tian Shung
N1 - Funding Information:
This work was supported by grants from the National Science Council , Taiwan ( NSC 96-2628-M-006-002 ) and National Cheng Kung University , Tainan, Taiwan ( OUA 95-3-2-021 ) awarded to T. S. Wu and Y.C. Shen (NSC 97-2320-B-077-004 - MY3). This study was also supported in part by a grant from the National Cancer Institute , NIH ( CA17625-32 ) awarded to K. H. Lee and by a grant from Taiwan Department of Health Clinical Trial and Research Center of Excellence ( DOH100-TD-B-111-004 ).
PY - 2012/1
Y1 - 2012/1
N2 - Chalcones have a distinctive 1,3-diarylpropenone skeleton and exert numerous biological effects. Using a one-step Claisen-Schmidt condensation, we synthesized eleven bis-chalcones (3-13) and three acetyl chalcones (14-16) from substituted aldehydes and diacetylresorcinol. The compounds were tested for in vitro cytotoxic activity against four human cancer cell lines (A549, DU145, KB, and KB-VIN) and inhibition of NO production in lipopolysaccharide (LPS)-activated microglial cells. Among them, four compounds (3, 5, 6, and 13) showed significant cytotoxic activity with EC 50 values ranging from 1.57 to 5.14 μM, and seven compounds (3, 5-8, 10, and 13) displayed potent anti-inflammatory activity by inhibiting NO production with IC 50 values ranging from 0.95 to 8.65 μM. A mechanism of action study of active compounds 6 and 7 discovered that these compounds down-regulated iNOS expression by inhibiting p65 NF-κB activation/nuclear translocation due to prevention of IκBα degradation. Structure-activity relationship (SAR) findings are also discussed.
AB - Chalcones have a distinctive 1,3-diarylpropenone skeleton and exert numerous biological effects. Using a one-step Claisen-Schmidt condensation, we synthesized eleven bis-chalcones (3-13) and three acetyl chalcones (14-16) from substituted aldehydes and diacetylresorcinol. The compounds were tested for in vitro cytotoxic activity against four human cancer cell lines (A549, DU145, KB, and KB-VIN) and inhibition of NO production in lipopolysaccharide (LPS)-activated microglial cells. Among them, four compounds (3, 5, 6, and 13) showed significant cytotoxic activity with EC 50 values ranging from 1.57 to 5.14 μM, and seven compounds (3, 5-8, 10, and 13) displayed potent anti-inflammatory activity by inhibiting NO production with IC 50 values ranging from 0.95 to 8.65 μM. A mechanism of action study of active compounds 6 and 7 discovered that these compounds down-regulated iNOS expression by inhibiting p65 NF-κB activation/nuclear translocation due to prevention of IκBα degradation. Structure-activity relationship (SAR) findings are also discussed.
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U2 - 10.1016/j.ejmech.2011.10.026
DO - 10.1016/j.ejmech.2011.10.026
M3 - Article
C2 - 22115618
AN - SCOPUS:84855778053
SN - 0223-5234
VL - 47
SP - 97
EP - 103
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
IS - 1
ER -