Abstract
A series of novel 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione derivatives were synthesized and evaluated for their inhibitory effects on osteoclast activities by using TRAP-staining assay. Among the tested compounds, 3d and 3h exhibited more potent osteoclast-inhibitory activities than the lead compound NDMC503 (a ring-fused structure of NDMC101), as reported in our previous study. Both 3d and 3h exhibited two-fold increase in activity compared to NDMC503. In addition, our biological results indicated that 3d and 3h could suppress RANKL-induced osteoclastogenesis-related marker genes, such as NFATc1, c-fos, TRAP, and cathepsin K. Notably, 3d could significantly attenuate the bone-resorbing activity of osteoclasts in the pit formation assay. Thus, this study might provide a new class of lead structures that warrant further development as potential anti-resorptive agents.
| Original language | English |
|---|---|
| Pages (from-to) | 4522-4532 |
| Number of pages | 11 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 23 |
| Issue number | 15 |
| DOIs | |
| Publication status | Published - Jul 23 2015 |
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Keywords
- NDMC101
- Osteoclastogenesis
- Pit formation assay
- RANKL
- TRAP-staining assay
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
- Molecular Biology
- Molecular Medicine
- Organic Chemistry
- Drug Discovery
- Pharmaceutical Science
Cite this
Novel inhibitors of RANKL-induced osteoclastogenesis : Design, synthesis, and biological evaluation of 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-diones. / Lee, Chia Chung; Liu, Fei Lan; Chen, Chun Liang; Chen, Tsung Chih; Liu, Feng Cheng; Ahmed Ali, Ahmed Atef; Chang, Deh Ming; Huang, Hsu Shan.
In: Bioorganic and Medicinal Chemistry, Vol. 23, No. 15, 23.07.2015, p. 4522-4532.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel inhibitors of RANKL-induced osteoclastogenesis
T2 - Design, synthesis, and biological evaluation of 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-diones
AU - Lee, Chia Chung
AU - Liu, Fei Lan
AU - Chen, Chun Liang
AU - Chen, Tsung Chih
AU - Liu, Feng Cheng
AU - Ahmed Ali, Ahmed Atef
AU - Chang, Deh Ming
AU - Huang, Hsu Shan
PY - 2015/7/23
Y1 - 2015/7/23
N2 - A series of novel 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione derivatives were synthesized and evaluated for their inhibitory effects on osteoclast activities by using TRAP-staining assay. Among the tested compounds, 3d and 3h exhibited more potent osteoclast-inhibitory activities than the lead compound NDMC503 (a ring-fused structure of NDMC101), as reported in our previous study. Both 3d and 3h exhibited two-fold increase in activity compared to NDMC503. In addition, our biological results indicated that 3d and 3h could suppress RANKL-induced osteoclastogenesis-related marker genes, such as NFATc1, c-fos, TRAP, and cathepsin K. Notably, 3d could significantly attenuate the bone-resorbing activity of osteoclasts in the pit formation assay. Thus, this study might provide a new class of lead structures that warrant further development as potential anti-resorptive agents.
AB - A series of novel 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione derivatives were synthesized and evaluated for their inhibitory effects on osteoclast activities by using TRAP-staining assay. Among the tested compounds, 3d and 3h exhibited more potent osteoclast-inhibitory activities than the lead compound NDMC503 (a ring-fused structure of NDMC101), as reported in our previous study. Both 3d and 3h exhibited two-fold increase in activity compared to NDMC503. In addition, our biological results indicated that 3d and 3h could suppress RANKL-induced osteoclastogenesis-related marker genes, such as NFATc1, c-fos, TRAP, and cathepsin K. Notably, 3d could significantly attenuate the bone-resorbing activity of osteoclasts in the pit formation assay. Thus, this study might provide a new class of lead structures that warrant further development as potential anti-resorptive agents.
KW - NDMC101
KW - Osteoclastogenesis
KW - Pit formation assay
KW - RANKL
KW - TRAP-staining assay
UR - http://www.scopus.com/inward/record.url?scp=84937817628&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937817628&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2015.06.007
DO - 10.1016/j.bmc.2015.06.007
M3 - Article
C2 - 26081760
AN - SCOPUS:84937817628
VL - 23
SP - 4522
EP - 4532
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 15
ER -