| Full text | |
| Author(s): |
Cunha, Micael Rodrigues
[1, 2]
;
Bhardwaj, Rajesh
[3]
;
Carrel, Aline Lucie
[1]
;
Lindinger, Sonja
[4]
;
Romanin, Christoph
[4]
;
Parise-Filho, Roberto
[2]
;
Hediger, Matthias A.
[3]
;
Reymond, Jean-Louis
[1]
Total Authors: 8
|
| Affiliation: | [1] Univ Bern, Dept Chem & Biochem, Freiestr 3, CH-3012 Bern - Switzerland
[2] Univ Sao Paulo, Dept Pharm, Prof Lineu Prestes Ave 580, BR-05508000 Sao Paulo - Brazil
[3] Inselspital Bern, Univ Hosp Bern, Dept Hypertens & Nephrol, CH-3010 Bern - Switzerland
[4] Johannes Kepler Univ Linz, Inst Biophys, Gruberstr 40, A-4020 Linz - Austria
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | RSC MEDICINAL CHEMISTRY; v. 11, n. 9, p. 1032-1040, SEP 1 2020. |
| Web of Science Citations: | 1 |
| Abstract | |
Transient receptor potential vanilloid 6 (TRPV6) is a calcium channel implicated in multifactorial diseases and overexpressed in numerous cancers. We recently reported the phenyl-cyclohexyl-piperazinecis-22aas the first submicromolar TRPV6 inhibitor. This inhibitor showed a seven-fold selectivity against the closely related calcium channel TRPV5 and no activity on store-operated calcium channels (SOC), but very significant off-target effects and low microsomal stability. Here, we surveyed analogues incorporating structural features of the natural product capsaicin and identified 3OG, a new oxygenated analog with similar potency against TRPV6 (IC50= 0.082 +/- 0.004 mu M) and ion channel selectivity, but with high microsomal stability and very low off-target effects. This natural product-inspired inhibitor does not exhibit any non-specific toxicity effects on various cell lines and is proposed as a new tool compound to test pharmacological inhibition of TRPV6 mediated calcium flux in disease models. (AU) | |
| FAPESP's process: | 13/19311-6 - Design, synthesis and antitumor activity of aryl-sulfonylhydrazone compounds |
| Grantee: | Thais Batista Fernandes |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 17/00689-0 - New antineoplastic agents: synthesis, molecular docking and antitumoral activity of capsaicinoids analogues |
| Grantee: | Roberto Parise Filho |
| Support Opportunities: | Regular Research Grants |