Journal article

The Synthesis and Biological Evaluation of Some C-9 and C-10 Substituted Derivatives of the RNA Polymerase I Transcription Inhibitor CX-5461

Madushani Amarasiri, Yen Vo, Michael G Gardiner, Perlita Poh, Priscilla Soo, Megan Pavy, Nadine Hein, Rita Ferreira, Katherine M Hannan, Ross D Hannan, Martin G Banwell

AUSTRALIAN JOURNAL OF CHEMISTRY | CSIRO PUBLISHING | Published : 2021

Abstract

The regio-isomeric alkynyl-substituted derivatives, 2 and 3, of the RNA Polymerase I (Pol I) transcription inhibitor CX-5461 (1) were prepared and the active one (compound 3) subjected to click reactions ([3 + 2]-cycloaddition reactions) with certain alkyl azides bearing biotin or fluorescent tags. Compounds 2 and 3, as well as four [3 + 2]-cycloadducts of the latter, were subjected to biological evaluation in a human acute myeloid leukemia cell line model. Among the six compounds tested only alkyne 3 remained active but this was less potent than parent 1.

Grants

Awarded by National Health and Medical Research Grants and Fellowships


Funding Acknowledgements

The authors thank the Australian Research Council for financial support. Nadine Hein, Rita Ferreira, Katherine M. Hannan, and Ross D. Hannan were supported by National Health and Medical Research Grants and Fellowships: #116999; #1100654; 1158732; #1158726##2002741.