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The synthesis and anti-proliferative effects of beta-elemene derivatives with mTOR inhibition activity
Liying Xu1, Shujuan Tao, Xianming Wang
1School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Abstract:
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.
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