PUBLICATION
Efficacy, Mechanism, and Structure-Activity Relationship of 6-Methoxy Benzofuran Derivatives as a Useful Tool for Senile Osteoporosis
- Authors
- Zhou, Z.Y., Sun, L.Q., Han, X.Y., Wang, Y.J., Xie, Z.S., Xue, S.T., Li, Z.R.
- ID
- ZDB-PUB-230121-4
- Date
- 2023
- Source
- Journal of medicinal chemistry 66(3): 1742-1760 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Benzofurans*/chemistry
- Benzofurans*/pharmacology
- Benzofurans*/therapeutic use
- Mice
- Osteoblasts
- Osteogenesis
- Osteoporosis*/drug therapy
- Osteoporosis*/prevention & control
- Rats
- Structure-Activity Relationship
- Zebrafish
- PubMed
- 36662031 Full text @ J. Med. Chem.
Citation
Zhou, Z.Y., Sun, L.Q., Han, X.Y., Wang, Y.J., Xie, Z.S., Xue, S.T., Li, Z.R. (2023) Efficacy, Mechanism, and Structure-Activity Relationship of 6-Methoxy Benzofuran Derivatives as a Useful Tool for Senile Osteoporosis. Journal of medicinal chemistry. 66(3):1742-1760.
Abstract
Most patients with senile osteoporosis (SOP) are severely deficient in bone mass, and treatments using bone resorption inhibitors, such as bisphosphonates, have shown limited efficacy. Small-molecule osteogenesis-promoting drugs are required to improve the treatment for this disease. Previously, we demonstrated that a compound with a benzofuran-like structure promoted bone formation by upregulating BMP-2, and it exhibited a therapeutic effect in SAMP-6 mice, glucocorticoid-induced osteoporosis rats, and ovariectomized rats. In this study, aged C57 and SAMP-6 mice models were used to investigate the therapeutic and preventive effects of compound 125 on SOP. scRNA-seq analysis showed that BMP-2 upregulation is the mechanism through which 125 accelerates bone turnover and increases the proportion of osteoblasts. We evaluated the structure-activity relationship of the candidate drugs and found that the derivative I-9 showed significantly higher efficacy than 125 and teriparatide in the zebrafish osteoporosis model. This study provides a foundation for the development of SOP drugs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping