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Chalcones, inhibitors for topoisomerase I and cathepsin B and L, as potential anti-cancer agents.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2013 Jun 01; Vol. 23 (11), pp. 3320-4. Date of Electronic Publication: 2013 Apr 05. - Publication Year :
- 2013
-
Abstract
- In order to diversify the pharmacological activity of chalcones and extend the scaffold of topoisomerase and cathepsins B and L inhibitors, we have designed and synthesized total 18 chalcone compounds and tested their biological activity. In the topoisomerase inhibition test, most analogues in group III and IV except compound 11 exhibited more efficient topoisomerase I inhibitory activity than camptothecin at 20 μM. Compounds 15, 16 and 18 in group IV showed significant cathepsin B and L inhibitory activity. Among the compounds, compound 15 was most active with IC50 values of 1.81±0.05 μM on cathepsin B and 3.15±0.07 μM on cathepsin L, respectively. Compound 15 also showed most potent cytotoxic activity against T47D and SNU638 cells with IC50 values of 1.37±0.05 μM and 0.62±0.01 μM, respectively. Overall, although more compounds should be tested and analyzed for clear SAR against topoisomerase I and cathepsin B and L, compound 15 showed consistent inhibitory ability on the tested assays, which can implicate the cytotoxic activity of compound 15 on topoisomerase I and cathepsin B and L inhibitory pathways.<br /> (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Subjects :
- Antineoplastic Agents chemical synthesis
Antineoplastic Agents toxicity
Cathepsin B metabolism
Cathepsin L metabolism
Cell Line, Tumor
Cell Survival drug effects
Chalcones chemical synthesis
Chalcones toxicity
DNA Topoisomerases, Type I metabolism
DNA Topoisomerases, Type II chemistry
DNA Topoisomerases, Type II metabolism
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors toxicity
Humans
Structure-Activity Relationship
Topoisomerase I Inhibitors chemical synthesis
Topoisomerase I Inhibitors toxicity
Antineoplastic Agents chemistry
Cathepsin B antagonists & inhibitors
Cathepsin L antagonists & inhibitors
Chalcones chemistry
DNA Topoisomerases, Type I chemistry
Enzyme Inhibitors chemistry
Topoisomerase I Inhibitors chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 23
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 23608763
- Full Text :
- https://doi.org/10.1016/j.bmcl.2013.03.106