Rational design, synthesis and anti-inflammatory activity of 6-substituted dihydrobenzophenanthridine derivatives

a series of 6-substituted dihydrobenzophenanthridine alkaloids were synthesized by introduction of different functional groups to C-6 of dihydrobenzophenanthridine backbone. The preliminary anti-inflammatory activities of all compounds were screened by investigating the inhibitory ability on NO production in LPS-stimulated RAW 264.7 cells. Among synthesized compounds, 6-(N-phenyl)-aminocarbonyl methyl dihydrochelerythrine (compound 12b) showed increased anti-inflammatory ability and decreased cytotoxicity and could inhibit the expression of pro-inflammatory factors TNF-α and IL-6 in RAW 264.7 macrophages. The anti-inflammatory ability of compound 12b was further evaluated using DSS-induced mice colitis models based on colonic tissue damage assessment, histopathological assessment and immunohistochemical analysis. In vivo experiment revealed that compound 12b had good alleviating effect on acute colitis in mice. In conclusion, compound 12b may be a promising anti-inflammatory lead compound.