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.
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.
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