Background: Recently, we devoted to disclosing the antibacterial activities of enmein-type
Objective: Eleven new enmein-type diterpenoid derivatives with different substituents and drug-like properties
were designed and synthesized.
Method: The antimicrobial activities against E. coli, S. aureus, B. subtilis and M. albicans were disclosed. The
antiproliferative activities against human cancer Bel-7402, K562, MGC-803 and CaEs-17 cells and non-cancerous
L-02 cells were also measured by MTT method.
Results: The results revealed that enmein-type diterpenoids showed more promising activities against tested
gram-positive bacteria than gram-negative bacterium and fungus. Compound 9 with R of 2-quinolyl group
exhibited the strongest antimicrobial activities with MIC values of 7.81 µg/ml and 0.98 µg/ml against S. aureus and
B. subtilis, respectively. All the target derivatives exhibited superior cytotoxic activities to compounds 1 and 2
against tumor cells, and slight selectivity between cancerous cells and normal liver cells. Compound 12 with R of
3-(2-chloropyridyl) group and IC50 values of 0.7 µM, 0.9 µM, 0.8 µM and 2.0 µM agaist four tumor cells,
respectively, was selected for further mechanism study in Bel-7402 cell line.
Conclusion: Compound 12 could induce S phase cell cycle arrest and apoptosis at low concentrations via
mitochondria-related pathways. The effects of compound 12 on some apoptosis related proteins showed that CDK2
was up regulated and ATM and cyclin A1 were down-regulated which confirmed the apoptosis and cell cycle effects.