The synthesis of glycyrrhetinic acid derivatives containing a nitrogen heterocycle and their antiproliferative effects in human leukemia cells.
Fifteen novel glycyrrhetinic acid derivatives containing a nitrogen heterocycle at C-30 and with different A-ring substituents were designed and synthesized. All of these derivatives have improved antiproliferative effects against human HL-60 leukemia cells. Compounds with a cyano-enone functionality on the A-ring exhibit greater growth inhibitory effects, compared to those with a 2-hydroxymethylene-3-keto, an isoxazole, or a 2-cyano-3-keto group. N-(2-cyano-3,11-dioxoolean-1,12-dien-30-yl)-4-piperidyl piperidine (9b) was found to be two-fold more potent than methyl 2-cyano-3,11-dioxooleana-1,12- dien-30-oate (CDODO-Me-11).
Gao
Yuan
Y
Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Guo
Xin
X
Li
Xiaojing
X
Liu
Dan
D
Song
Dandan
D
Xu
Ye
Y
Sun
Ming
M
Jing
Yongkui
Y
Zhao
Linxiang
L
D000969:Antinematodal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D006034:Glycyrrhetinic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure
D000969:Antinematodal Agents; D006034:Glycyrrhetinic Acid