Design and synthesis of pyrido[3,2-α]carbazole derivatives and their analogues as potent antitumour agents

• A series of pyrido[3,2-α]carbazole derivatives and their analogues were synthesized.
• One novel and rapid synthetic approach is described.
• Synthesized compounds were evaluated against A549 and HT29 cell lines.
• Most compounds were found to be very potent, especially compound 24.

A series of pyrido[3,2-α]carbazole derivatives and their analogues have been prepared and evaluated for their antitumour activity against human lung cancer A549 cells and colon cancer HT29 cells. The intermediates 4a–4k are successfully synthesized from 1a–1k and ethyl 2-(3-bromopyridin-2-yl)acetate by Knoevenagel condensation and intramolecular Heck-type reaction, and this is a novel and efficient synthetic approach to the core scaffold of the target compounds. These target compounds have shown an interesting antitumour profile towards the tested cell lines with IC50 values ranging from 0.07 μM to 4.45 μM. Among all the compounds synthesized, 8 compounds show higher potency than R16, 12 compounds are as potent as R16, and 6 compounds are less potent than R16. The best compound 24 is 7 times and approximately 10 times as potent as R16 against A549 and HT29 cells, respectively.

Synthesis and antitumour activity of a series of pyrido[3,2-α]carbazole derivatives/their analogues are presented. Compound 24 proved to be more potent than anti-MDR agent R16 against A549 and HT29 cells. Moreover, one novel and efficient synthetic approach to the core structure via Knoevenagel condensation and intramolecular Heck-type reaction is also described.Figure optionsDownload as PowerPoint slide