Synthesis of budesonide conjugates and their anti-inflammatory effects: a preliminary study.

Abstract

PURPOSE:

Budesonide (Bud) is a nonhalogenated glucocorticoid with high anti-inflammatory potency and low systemic side effects. However, the poor water solubility of Bud affects its dissolution and release behavior, thus influencing its anti-inflammatory effect. This study was aimed at synthesizing and evaluating novel conjugates of Bud, hoping to increase the anti-inflammatory activity of Bud by improving its water solubility.

MATERIALS AND METHODS:

Seven novel Bud conjugates (3a-3g) were designed and synthesized in this study. Besides, the equilibrium solubility, cell viability, in vitro and in vivo anti-inflammatory activity, and the hydrolysis behavior of the conjugates in different pH solutions, rat and human plasma, and rat lung homogenate were studied in detail.

RESULTS:

As compared to Bud, the equilibrium solubility of 3a, 3c, and 3e was significantly increased; 3a, 3b, and 3c significantly inhibited the interleukin-6 production in lipopolysaccharide-induced A549 cells; 3a and 3e could significantly decrease the xylene-induced ear edema; and 3a and 3c were gradually and slowly hydrolyzed into Bud in the alveolar fluid and lung homogenate and broken down quickly in plasma.

CONCLUSION:

The amino acid ester compounds budesonide-21-glycine ester (3a) and budesonide-21-alanine ester (3c) were selected as potential conjugates of Bud. This study would provide a theoretical and an experimental basis for the in vivo process of glucocorticoids and the treatment of inflammatory diseases.

• Authors: Yan Yan, Pengchong Wang, Ruiying Li, Ying Sun, Rui Zhang, Chuanchuan Huo, Jianfeng Xing, Yalin Dong
• Journal: Drug design, development and therapy (Drug Des Devel Ther) Vol. 13 Pg. 681-694 ( 2019) ISSN: 1177-8881 [Electronic] New Zealand
• PMID: 30858698 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Interleukin-6
• Xylenes
• Budesonide

Topics

• A549 Cells
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemical synthesis, chemistry, pharmacology)
• Budesonide (chemical synthesis, chemistry, pharmacology)
• Cell Survival (drug effects)
• Ear Diseases (chemically induced, drug therapy)
• Edema (chemically induced, drug therapy)
• Humans
• Interleukin-6 (antagonists & inhibitors, biosynthesis)
• Male
• Mice
• Mice, Inbred Strains
• Molecular Structure
• Rats
• Rats, Sprague-Dawley
• Structure-Activity Relationship
• Xylenes