Design, Synthesis, and Antitumor Evaluation of the Conjugates of Berberine and Dehydrocostus Lactone

Berberine and dehydrocostus lactone have been identified as lead compounds exhibiting significant antitumor activity. Following the combination principle of drug design, conjugate homologs of berberine and dehydroxylone lactone were synthesized through selective demethylation, substitution reactions, and Michael addition reactions. The structures of the resulting products were verified using proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and electrospray ionization-mass spectrometry. The inhibitory effects of the target compounds on the proliferation of four tumor cell lines, MHCC97H, HCC827, HELA, and HEL, in vitro were evaluated by the MTT method. The results showed that the inhibitory effects of the target compounds on the proliferation of the four tumor cell lines were much greater than those of the raw materials berberine and dehydrocostus lactone. In addition, the antitumor activity was enhanced with the prolongation of the carbon chain, and the inhibitory effects of the target compounds E3 against MHCC97H cells, with an IC50 = 0.995 ? 0.02, and against HCC827, with an IC50 = 3.46 ? 1.12. Furthermore, the inhibitory effects of the target compound E3 against MHCC97H cells were comparable to those of the positive control drugs and are expected to be potential antitumor drug candidates..