1154-82-1Relevant academic research and scientific papers
Amiloride as a new RNA-binding scaffold with activity against HIV-1 TAR
Patwardhan, Neeraj N.,Ganser, Laura R.,Kapral, Gary J.,Eubanks, Christopher S.,Lee, Janghyun,Sathyamoorthy, Bharathwaj,Al-Hashimi, Hashim M.,Hargrove, Amanda E.
supporting information, p. 1022 - 1036 (2017/07/12)
Diversification of RNA-targeted scaffolds offers great promise in the search for selective ligands of therapeutically relevant RNA such as HIV-1 TAR. We herein report the establishment of amiloride as a novel RNA-binding scaffold along with synthetic routes for combinatorial C(5)- and C(6)-diversification. Iterative modifications at the C(5)- and C(6)-positions yielded derivative 24, which demonstrated a 100-fold increase in activity over the parent dimethylamiloride in peptide displacement assays. NMR chemical shift mapping was performed using the 2D SOFAST-[1H-13C] HMQC NMR method, which allowed for facile and rapid evaluation of binding modes for all library members. Cheminformatic analysis revealed distinct differences between selective and non-selective ligands. In this study, we evolved dimethylamiloride from a weak TAR ligand to one of the tightest binding selective TAR ligands reported to date through a novel combination of synthetic methods and analytical techniques. We expect these methods to allow for rapid library expansion and tuning of the amiloride scaffold for a range of RNA targets and for SOFAST NMR to allow unprecedented evaluation of small molecule:RNA interactions.
Production of new amilorides as potent inhibitors of mitochondrial respiratory complex I
Murai, Masatoshi,Habu, Sayako,Murakami, Sonomi,Ito, Takeshi,Miyoshi, Hideto
, p. 1061 - 1066 (2015/10/05)
Amilorides, well-known inhibitors of Na+/H+ antiporters, have also shown to inhibit bacterial and mitochondrial NADH-quinone oxidoreductase (complex I). Since the membrane subunits ND2, ND4, and ND5 of bovine mitochondrial complex I
