Discovery of Salidroside-Derivated Glycoside Analogues as Novel Angiogenesis Agents to Treat Diabetic Hind Limb Ischemia.
J Med Chem
; 65(1): 135-162, 2022 01 13.
Article
in En
| MEDLINE
| ID: mdl-34939794
ABSTRACT
Therapeutic angiogenesis is a potential therapeutic strategy for hind limb ischemia (HLI); however, currently, there are no small-molecule drugs capable of inducing it at the clinical level. Activating the hypoxia-inducible factor-1 (HIF-1) pathway in skeletal muscle induces the secretion of angiogenic factors and thus is an attractive therapeutic angiogenesis strategy. Using salidroside, a natural glycosidic compound as a lead, we performed a structure-activity relationship (SAR) study for developing a more effective and druggable angiogenesis agent. We found a novel glycoside scaffold compound (C-30) with better efficacy than salidroside in enhancing the accumulation of the HIF-1α protein and stimulating the paracrine functions of skeletal muscle cells. This in turn significantly increased the angiogenic potential of vascular endothelial and smooth muscle cells and, subsequently, induced the formation of mature, functional blood vessels in diabetic and nondiabetic HLI mice. Together, this study offers a novel, promising small-molecule-based therapeutic strategy for treating HLI.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenols
/
Angiogenesis Inducing Agents
/
Diabetes Mellitus, Experimental
/
Glucosides
/
Glycosides
/
Hindlimb
/
Ischemia
/
Neovascularization, Pathologic
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2022
Document type:
Article
Affiliation country:
China