- Title
- Parallel solution-phase synthesis of targeted tyrphostin libraries with anticancer activity
- Creator
- Hill, Timothy A.; Sakoff, Jennette A.; Robinson, Phillip J.; McCluskey, Adam
- Relation
- Australian Journal of Chemistry Vol. 58, Issue 2, p. 94-103
- Publisher Link
- http://dx.doi.org/10.1071/CH04143
- Publisher
- CSIRO Publishing
- Resource Type
- journal article
- Date
- 2005
- Description
- 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.
- Subject
- semi-automation; elegant synthesis; parallel solution-phase synthesis; anticancer activity
- Identifier
- uon:1723
- Identifier
- http://hdl.handle.net/1959.13/27489
- Identifier
- ISSN:0004-9425
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