Microbial and chemical transformations of euphorbia factor L1 and the P-glycoprotein inhibitory activity in zebrafishes.

Abstract

Euphorbia factor L1 (EFL1, 1) is a natural tri-ester of 6,17-epoxylathyrol with cancer multidrug resistance (MDR) reversal activity. Several EFL1 derivatives (2-9) were prepared by chemical and microbial transformations and their ability to inhibit P-glycoprotein (P-gp) activity was estimated. Six de-acylated derivatives (2-7) were obtained through base-hydrolysis of 1, and the base-catalysed hydrolysis via KOH and NaOH yielded different hydrolysed products of 1. Two biotransformed products (8-9) were directly obtained via microbial transformation of 1, and 8 was also formed by microbial conversion of the hydrolysed product 3. The P-gp modulation of 1-9 was assessed by a zebrafish model. The substrate 1 and its biotransformed product 9 as the tri-esters of lathyranes possessed the highest P-gp inhibitory activity with IC50 values of 34.97 and 15.50 µM, respectively, through down-regulating P-gp expression at the protein level rather than at MDR1 mRNA level.

• Authors: Xin Liu, Zhihong Cheng
• Journal: Natural product research (Nat Prod Res) Vol. 37 Issue 6 Pg. 871-881 (Mar 2023) ISSN: 1478-6427 [Electronic] England
• PMID: 35776104 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• euphorbia factor L1
• Diterpenes

Topics

• Animals
• Zebrafish (metabolism)
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics, metabolism)
• Drug Resistance, Multiple
• Diterpenes (pharmacology)
• Drug Resistance, Neoplasm
• Euphorbia (metabolism)