Abstract:
The novel oleanolic acid derivatives
2a-2e were synthesized by introducing an
α, β-unsaturated ketone moiety to C-ring of oleanolic acid(OA)via a nine-step reaction sequence, yielding an active CDDO-Me analogue(
1 ), followed by coupling of C3-OH of
1 with various aliphatic and aromatic carboxylic acids, respectively. Derivatives
3a-3e were synthesized by substituting C-1 of compounds
2a-2e with bromine. The target compounds were characterized by IR, MS and
1H NMR spectra. All the target compounds showed strong inhibitory effects against two tumor cell lines(HepG2 and A549)to a varying extent. The anti-proliferative activities of active compounds
3b and
3c (IC
50=6. 13±1. 16 μmol/L and IC
50=5. 49±1. 03 μmol/L, respectively)against HepG2 and A549 were more potent than compound
1 and comparable to the positive control CDDO-Me. In addition, all the target compounds displayed much weaker anti-proliferative activity against the two tumor cell lines than that against normal BEAS-2B cells. Compound
3c showed ten-fold selective inhibition against HepG2 relative to BEAS-2B cells, and is thus worthy of further study.