Abstract
Transmembrane protein 16A (TMEM16A) channels are recently discovered membrane proteins that functions as a calcium activated chloride channel (CaCC). CaCCs are major regulators of various physiological processes, such as sensory transduction, epithelial secretion, smooth muscle contraction and oocyte fertilization. Thirty novel 5-substituted benzyloxy-2-arylbenzofuran-3- carboxylic acids (B01-B30) were synthesized and evaluated for their TMEM16A inhibitory activity by using short circuit current measurements in Fischer rat thyroid (FRT) cells expressing human TMEM16A. IC 50 values were calculated using YFP fluorescence plate reader assay. Final compounds, having free carboxylic group displayed significant inhibition. Eight of the novel compounds B02, B13, B21, B23, B25, B27, B28, B29 exhibit excellent CaCCs inhibition with IC 50 value <6 μM, with compound B25 exhibiting the lowest IC 50 value of 2.8 ± 1.3 μM. None of the tested ester analogs of final benzofuran derivatives displayed TMEM16A/CaCCs inhibition.
| Original language | English |
|---|---|
| Pages (from-to) | 4237-4244 |
| Number of pages | 8 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 20 |
| Issue number | 14 |
| DOIs | |
| Publication status | Published - 2012 Jul 15 |
Bibliographical note
Funding Information:One of the authors (S.K.) is grateful to University Grants Commission (UGC), New Delhi, India for financial support and award of Senior Research Fellowship. The authors are thankful to Mr. Jared W. Rigoli, Mr. Joe D. Rigoli and Ms. Ali Heckman for their help in purification of compounds.
All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry