Russian Journal of BiotherapyRussian Journal of BiotherapyРоссийский биотерапевтический журнал1726-97841726-9792Publishing House ABV Press85610.17650/1726-9784-2017-16-1-61-69ORIGINAL REPORTSОРИГИНАЛЬНЫЕ СТАТЬИANTI-TUMOR EFFECT OF CPDA ENANTIOMERS IN VITRO IN THE MODEL OF ACUTE LYMPHOBLASTIC LEUKEMIAПРОТИВООПУХОЛЕВЫЙ ЭФФЕКТ ЭНАНТИОМЕРОВ CPDA IN VITRO НА МОДЕЛИ ОСТРОГО ЛИМФОБЛАСТНОГО ЛЕЙКОЗАSavinkovaA. V.СавинковаА. В.
Russian Federation
TilovaL. R.ТиловаЛ. Р.
Russian Federation
BorisovaO. I.БорисоваО. И.
Russian Federation
ZhidkovaE. M.ЖидковаЕ. М.
Russian Federation
KuzinK. A.КузинК. А.
Russian Federation
KirsanovK. I.КирсановК. И.
Russian Federation
BelitskyG. A.БелицкийГ. А.
Russian Federation
BudunovaI. V.БудуноваИ. В.
Russian Federation
YakubovskayaM. G.ЯкубовскаяМ. Г.
Russian Federation
LesovayaE. A.ЛесоваяЕкатерина Андреевна
Russian Federation
lesovenok@yandex.ruN.N. Blokhin Russian Cancer Research CenterФГБУ«Российский онкологический научный центр им. Н.Н. Блохина» Минздрава РоссииMoscow Technological UniversityМосковский технологический университетNorthwestern UniversityСеверо-Западный университетRyazan State Medical University named after academician I.P. PavlovРязанский государственный медицинский университет им. И.П. Павлова30032017161616910042018https://bioterapevt.abvpress.ru/jour/article/view/856

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.

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