The synthesis and anti-proliferative effects of beta-elemene derivatives with mTOR inhibition activity.
Fourteen beta-elemene derivatives containing a piperazine, a morpholine, a tetrahydropyrrole, a thiophenylethylamine, or a cyclohexamine group were synthesized. The structures of these beta-elemene derivatives were characterized with IR, 1H NMR, MS, and elemental analyses. All these derivatives had an increased anti-proliferative activity in human cervix epitheloid carcinoma HeLa, gastric carcinoma SGC-7901, and leukemia K562 cells comparing with that of beta-elemene. Among these derivatives, 13,14-bis(cis-3,5-dimethyl-1-piperazinyl)-beta-elemene (IIi), 13,14-bis[2-(2-thiophenyl)ethylamino]-beta-elemene (IIm), and 13,14-bis(cyclohexamino)-beta-elemene (IIn) were the most potent agents. IIi, IIm, and IIn inhibited K562 cell growth with an IG50 below 5 microM that was correlated with mTOR activity inhibition.
Xu
Liying
L
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Tao
Shujuan
S
Wang
Xianming
X
Yu
Zhiying
Z
Wang
Minwei
M
Chen
Duo
D
Jing
Yongkui
Y
Dong
Jinhua
J
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D011494:Protein Kinases / Q000187:drug effects*; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D058570:TOR Serine-Threonine Kinases
D012717:Sesquiterpenes; C445979:beta-elemene; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases