Anti-Tumor Effect of Cpda Enantiomers in Vitro in the Model of Acute Lymphoblastic Leukemia

Abstract

Introduction. Glucocorticoids are the important component of combined chemotherapy of blood cancer. Therapeutic effects of glucocorticoids is realized via activation of glucocorticoid receptor transrepression, the development of side effects is associated with transactivation. We demonstrated earlier that compound belonging the class of selective glucocorticoid receptor agonists, CpdA, selectively induced transrepression in blood cancer cells. CpdA represents a mixture of two enantiomers, which can differ in interaction with the receptor. Aim. The main aim of present study was to synthesize CpdA enantiomers and to evaluate their biological properties. Materials and methods. Synthesis was carried out based on Sharpless dihydroxylation; anti-tumor activity in vitro was evaluated by antiproliferative and pro-apoptotic effects. Ligand properties were estimated by PCR-analysis of glucocorticoid- and NF-kB-dependent genes expression. Results and conclusions. We demonstrated that CpdA enantiomers revealed anti-tumor activity in vitro and did not induce transactivation. Moreover, S-enantiomer of CpdA in the most tests demonstrated more pronounced activity and is more perspective molecule for future studies in vivo.

Synephrine and Its Derivative Compound A: Common and Specific Biological Effects

“…Of note, CpdA enantiomers slightly differ in their biological effects from a racemic mixture. In our previous studies, we synthesized CpdA enantiomers, and in our in vitro studies S-CpdA was revealed to exert stronger proapoptotic effects on leukemia cells as compared to R-CpdA [41]. The p-synephrine isomer is widely used as a dietary supplement for weight loss since it promotes fat oxidation [1,6].…”

“…CpdA, a well-characterized SEGRA, is a synthetic analog of a natural compound found in Salsola tuberculatiformis Botschantzev and exerts GR-dependent anti-inflammatory and anti-cancer effects [16,41,62,63]. CpdA appears to be a promising alternative to GCs with fewer side effects [18,41,51,62,[64][65][66].…”