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RESEARCH ARTICLE
Contents Vol 74(7)

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 A , Yen Vo A , Michael G. Gardiner A , Perlita Poh B , Priscilla Soo B , Megan Pavy B , Nadine Hein B , Rita Ferreira B , Katherine M. Hannan B , Ross D. Hannan B C D E F H and Martin G. Banwell https://orcid.org/0000-0002-0582-475X A G H
+ Author Affiliations
- Author Affiliations

A Research School of Chemistry, Institute of Advanced Studies, The Australian National University, Canberra, ACT 2601, Australia.

B ACRF Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia.

C Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Vic. 3010, Australia.

D Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Vic. 3000, Australia.

E Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic. 3800, Australia.

F School of Biomedical Sciences, University of Queensland, Brisbane, Qld 4072, Australia.

G Institute for Advanced and Applied Chemical Synthesis, Jinan University, Guangzhou 510632, China.

H Corresponding authors. Email: Ross.Hannan@anu.edu.au; Martin.Banwell@anu.edu.au

Australian Journal of Chemistry 74(7) 540-556 https://doi.org/10.1071/CH21049
Submitted: 16 February 2021  Accepted: 16 March 2021   Published: 16 April 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.

Keywords: alkyne, azide, biotin, cancer, click chemistry, fluorescent, ribosomal RNA, RNA Polymerase 1 inhibitor, synthesis, tagging.


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