Design,synthesis and biological activity evaluation of water-soluble borneol phosphate prodrug
10.11665/j.issn.1000-5048.2023060703
- VernacularTitle:水溶性冰片磷酸酯前药的设计、合成及生物活性评价
- Author:
Lulu ZHANG
1
;
Meiling SUN
;
Yajuan QIN
;
Tingyou LI
Author Information
1. 南京医科大学药学院,南京 211166
- Keywords:
borneol;
phosphate;
ischemic stroke;
improved water solubility
- From:
Journal of China Pharmaceutical University
2024;55(3):375-380
- CountryChina
- Language:Chinese
-
Abstract:
In this study,structural optimization of borneol was carried out to improve their solubility and promote their further application in stroke therapy.BP-3,a prodrug of borneol,was designed and synthesized based on the principle of phosphate modification.The solubility of BP-3 was determined by evaporative light scattering detector(ELSD),and the degree and speed of drug release were tested in mouse plasma,and the neuroprotective effect of BP-3 was evaluated in mouse model of transient middle cerebral artery occlusion(tMCAO).According to the results,BP-3 was completely soluble in saline at 20 mg/mL;in mouse plasma,approximately 40%of the borneol were released within 2 h;in the tMCAO mouse model,TTC staining showed that BP-3 was effective in reducing the infarct area;Nissl staining showed that BP-3 ameliorated the neuronal injury;the grip and grasping strength tests elucidated that BP-3 reduced the damage of sports ability caused by injury;and the rotating rod test proved that BP-3 could promote the recovery of motor ability in mice.BP-3 has good water solubility,suitable drug release rate and excellent neuroprotective effects,and has broad prospects for drug development.
