Synthesis and anticancer activity of some novel indolo[3,2-b]andrographolide derivatives as apoptosis-inducing agents

• Novel indolo[3.2-b]andrographolide derivatives were designed and synthesized.
• In vitro cytotoxicities of all compounds were tested against three cell lines.
• 14 compounds showed better anti-cancer activities than 1 for all three cell lines.
• Compound 6l displayed best activity against all three cell lines.
• 6l blocked the cell cycle at S phase and induced the apoptosis of cells.

A series of novel indolo[3,2-b]andrographolide derivatives were designed, synthesized and screened in vitro against three human cancer cell lines MCF7 (human breast cancer), HCT116 (human colon cancer), and DU145 (human prostate cancer). Fourteen compounds 6b, 6e, 6i, 6j, 6l, 6m, 6n, 12a, 12b, 13a, 13b, 15a, 17a, and 17b exhibited better anti-cancer activities than andrographolide for all three human cancer lines, with compound 6l displaying best activity with IC50 values of 1.85, 1.22 and 1.24 μM against MCF7, HCT116 and DU145 respectively. Preliminary anti-cancer mechanistic investigation was performed in terms of the cell cycle arrest and cell apoptosis assays of compound 6l against HCT116 using flow cytometry, and the results suggested that compound 6l inhibited tumor proliferation through inducing early and late cellular apoptosis in a concentration-dependent manner and causing cell cycle arrest in the S-phase.

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