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

doi:10.1071/CH21049

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	540-556
Number of pages	17
Journal	Australian Journal of Chemistry
Volume	74
Issue number	7
DOIs	https://doi.org/10.1071/CH21049
Publication status	Published - 21 Jul 2021

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10.1071/CH21049

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title = "The Synthesis and Biological Evaluation of Some C-9 and C-10 Substituted Derivatives of the RNA Polymerase i Transcription Inhibitor CX-5461",

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 = "RNA Polymerase 1 inhibitor, alkyne, azide, biotin, cancer, click chemistry, fluorescent, ribosomal RNA, synthesis, tagging",

author = "Madushani Amarasiri and Yen Vo and Gardiner, {Michael G.} and Perlita Poh and Priscilla Soo and Megan Pavy and Nadine Hein and Rita Ferreira and Hannan, {Katherine M.} and Hannan, {Ross D.} and Banwell, {Martin G.}",

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doi = "10.1071/CH21049",

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AU - Amarasiri, Madushani

AU - Vo, Yen

AU - Gardiner, Michael G.

AU - Poh, Perlita

AU - Soo, Priscilla

AU - Pavy, Megan

AU - Hein, Nadine

AU - Ferreira, Rita

AU - Hannan, Katherine M.

AU - Hannan, Ross D.

AU - Banwell, Martin G.

PY - 2021/7/21

Y1 - 2021/7/21

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AB - 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.

KW - RNA Polymerase 1 inhibitor

KW - alkyne

KW - azide

KW - biotin

KW - cancer

KW - click chemistry

KW - fluorescent

KW - ribosomal RNA

KW - synthesis

KW - tagging

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U2 - 10.1071/CH21049

DO - 10.1071/CH21049

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SN - 0004-9425

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JF - Australian Journal of Chemistry

IS - 7

ER -

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

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