Parallel solution-phase synthesis of targeted tyrphostin libraries with anticancer activity

Hill, Timothy A., Sakoff, Jennette A., Robinson, Phillip J. and McCluskey, Adam (2005) Parallel solution-phase synthesis of targeted tyrphostin libraries with anticancer activity. Australian Journal of Chemistry, 58 2: 94-103. doi:10.1071/CH04143


Author Hill, Timothy A.
Sakoff, Jennette A.
Robinson, Phillip J.
McCluskey, Adam
Title Parallel solution-phase synthesis of targeted tyrphostin libraries with anticancer activity
Journal name Australian Journal of Chemistry   Check publisher's open access policy
ISSN 0004-9425 (print); 1448-0038 (electronic)
Publication date 2005-02-21
Sub-type Article (original research)
DOI 10.1071/CH04143
Volume 58
Issue 2
Start page 94
End page 103
Total pages 10
Editor Curt Wentrup
Place of publication Melbourne, Vic., Australia
Publisher Commonwealth Scientific and Industrial Research Organization (CSIRO) in co-operation with the Australian Academy of Science
Language eng
Subject 0304 Medicinal and Biomolecular Chemistry
1115 Pharmacology and Pharmaceutical Sciences
03 Chemical Sciences
Formatted abstract
The combination of semi-automation, an elegant synthesis, and parallel solution-phase synthesis approaches has allowed the development of five targeted, symmetrical tyrphostin compound libraries. These libraries on average are comprised of 12 compounds. Notwithstanding this, low micromolar potent growth inhibitors against HT29 (colorectal carcinoma) and G401 (renal carcinoma) cell lines were discovered. Additionally, significant SAR data was obtained. We noted that the most potent growth inhibitory activity was consistently observed for those analogues that possessed a 2-chlorophenyl (for 10: GI50 HT29 5.5 ± 0.4 μM, GI50 G401 2.6 ± 0.4 μM; for 23: GI50 HT29 2.4 ± 0.2 μM, GI50 G401 1.9 ± 1 μM; for 34: GI50 HT29 8.8 ± 3.1 μM, GI50 G401 6.2 ± 2.9 μM; for 46: GI50 HT29 5.2 ± 0.9 μM, GI50 G401 3.7 ± 0.6 μM; for 57: GI50 HT29 4.6 ± 0.8 μM, GI50 G401 2.1 ± 0.2 μM), a 3-chlorophenyl (for 11: GI50 HT29 3.8 ± 0.7 μM, GI50 G401 1.7 ± 0.7 μM; for 48: GI50 HT29 5.9 ± 0.1 μM, GI50 G401 3.4 ± 0.6 μM; for 58: GI50 HT29 4.8 ± 0.9 μM, GI50 G401 3.4 ± 0.2 μM), or a 3-methoxyphenyl substituent (for 13: GI50 HT29 7.4 ± 3.8 μM, GI50 G401 2.8 ± 0.5 μM; for 26: GI50 HT29 4.5 ± 0.5 μM, GI50 G401 4.9 ± 1 μM; for 37: GI50 HT29 3.7 ± 0.2 μM, GI50 G401 1.6 ± 0.2 μM; for 49: GI50 HT29 3.7 ± 0.4 μM, GI50 G401 3.4 ± 0.2 μM; for 60: GI50 HT29 4.1 ± 0.6 μM, GI50 G401 1.8 ± 0.3 μM). Finally, we noted that increasing the distance between the terminal aromatic rings had only a minimal effect on the 2-, 3-chlorophenyl, and 3-methoxyphenyl analogues, but did have a favourable effect on OH, COOH, and multiply substituted analogues.
©CSIRO 2005
Keyword Parallel solution-phase synthesis
Tyrphostin
HT29 (colorectal carcinoma)
G401 (renal carcinoma)
Colorectal carcinoma
Renal carcinoma
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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Created: Fri, 19 Feb 2010, 09:41:57 EST by June Temby on behalf of Institute for Molecular Bioscience