A Novel Betulinic Acid Analogue: Synthesis, Solubility, Antitumor Activity and Pharmacokinetic Study in Rats.

Abstract

Betulinic acid (BA) and betulin (BE) are naturally pentacyclic triterpenes with documented biological activities, especially antitumor and anti-inflammatory activity. However, their bioavailability in vivo is not satisfactory in terms of medical applications. Thus, to improve the solubility and bioavailability so as to improve the efficacy, 28-O-succinyl betulin (SBE), a succinyl derivative of BE, was synthesized and its solubility, in vitro and in vivo anti-tumor activities, the apoptosis pathway as well as the pharmacokinetic properties were investigated. The results showed that SBE exhibited significantly higher solubility in most of the tested solvents, and showed a maximum solubility of 7.19 ± 0.66 g/L in n-butanol. In vitro and in vivo anti-tumor activity assays indicated both BA and SBE exhibited good anti-tumor activities, and SBE demonstrated better potential compared to BA. An increase in the ratio of Bad/Bcl-xL and activation of caspase 9 was found in SBE treated Hela cells, suggesting that the intrinsic mitochondrial pathway is involved in SBE induced apoptosis. Compared with BA, SBE showed much-improved absorption and bioavailability in pharmacokinetic studies.

• Authors: Yucen Liang, Meixuan Zhu, Tao Xu, Weimin Ding, Min Chen, Yang Wang, Jian Zheng
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 28 Issue 15 (Jul 28 2023) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 37570685 (Publication Type: Journal Article)

Chemical References

• betulin
• Betulinic Acid
• Triterpenes
• Pentacyclic Triterpenes

Topics

• Humans
• Rats
• Animals
• Betulinic Acid
• HeLa Cells
• Solubility
• Triterpenes (pharmacology)
• Pentacyclic Triterpenes
• Cell Line, Tumor