Palindromic carbazole derivatives: unveiling their antiproliferative effect via topoisomerase II catalytic inhibition and apoptosis induction

Abstract

Human DNA topoisomerases are essential for crucial cellular processes, including DNA replication, transcription, chromatin condensation, and maintenance of its structure. One of the significant strategies employed in cancer treatment involves the inhibition of a specific type of topoisomerase, known as topoisomerase II (Topo II). Carbazole derivatives, recognised for their varied biological activities, have recently become a significant focus in oncological research. This study assesses the efficacy of three symmetrically substituted carbazole derivatives: 2,7-Di(2-furyl)-9H-carbazole (27a), 3,6-Di(2-furyl)-9H-carbazole (36a), and 3,6-Di(2-thienyl)-9H-carbazole (36b) – as anticancer agents. Among investigated carbazole derivatives, compound 3,6-di(2-furyl)-9H-carbazole bearing two furan moieties emerged as a novel catalytic inhibitor of Topo II. Notably, 3,6-di(2-furyl)-9H-carbazole effectively selectively inhibited the relaxation and decatenation activities of Topo IIα, with minimal effects on the IIβ isoform. These findings underscore the potential of compound 3,6-Di(2-furyl)-9H-carbazole as a promising lead candidate warranting further investigation in the realm of anticancer drug development.

Graphical Abstract

Keywords:

• Apoptosis
• cancer
• carbazole
• topoisomerase

Author contributions

Conceptualisation: M.O.; methodology: M.O., N.M., A.C, A.M.D., and M.Bi.; validation: M.O., A.C., and A.M.D.; formal analysis: M.O.; writing – original draft preparation: M.O. and N.M.; graphical conceptualisation: M.O. and N.M.; writing – review and editing: M.O., N.M., A.K., J.M.P., M.M., and M.B.

Disclosure statement

The authors report no conflicts of interest.

Data availability statement

The datasets presented in the current study are available from the corresponding author upon reasonable request.

Additional information

Funding

This work was financially supported by a grant from the National Centre for Research and Development STRATEGMED3/306853/9/NCBR/2017, Warsaw, Poland. The financial support to maintenance of research facilities used in these studies from Gdańsk University of Technology by the DEC – 2/2021/IDUB/V0.6/Si grant under the SILICIUM SUPPORTING CORE R&D FACILITIES – “Excellence Initiative – Research University” program is gratefully acknowledged.