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
- Publication Type:Journal Article
- Keywords:
borneol / phosphate / ischemic stroke / improved water solubility
- From:
Journal of China Pharmaceutical University
2024;55(3):375-380
- CountryChina
- Language:Chinese
-
Abstract:
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.
