Design and synthesis of mogrol derivatives modified on a ring with anti-inflammatory and anti-proliferative activities

A class of novel mogrol derivatives modified on A ring were synthesized. The screening result showed that indole-fused derivatives exhibited lower toxicity and better anti-inflammatory activity in LPS-induced RAW 264.7 cells model than mogrol and other compounds. Derivative B8 exerted superior inhibitory result of NO production (IC50 = 5.05 mu M) and inhibitory ability of TNF-alpha and IL-6 secretion to mogrol through iNOS/NF--KB pathway. Besides, the CCK8 assay was performed to evaluate their anti-proliferative activity against non-small cell lung cancer including A549, NCI-H460, H1299 and H1975 cells. Compared with mogrol, compound B8 showed moderate anti-proliferative activities against A549 and H1975 cells, while derivatives bearing alpha, beta-unsaturated ketone scaffold displayed broad-spectrum growth inhibition against four cell lines. Among them, compound A9 showed 12-fold higher activity than mogrol against H1299 and H1975 cells. The suppressive effect on expression level of p-p65 might account for the compound A9-induced growth inhibition and cell cycle arrest at G1 phase.

Automated summary

A class of novel mogrol derivatives has been synthesized and found to exhibit promising activity in anti-inflammatory and anti-proliferative effects. One derivative showed superior inhibitory activity against cell secretions and antioxidants through a specific pathway, while other derivatives displayed broad-spectrum activity in suppressing different types of lung cancer cell proliferation.