title: Sodium hydrogen exchanger inhibitory activity of benzotriazole derivatives.
abstract: Series of benzotriazole derivatives were synthesized and evaluated for their Sodium hydrogen exchanger-1 inhibitory potential. All compounds inhibit Sodium hydrogen exchanger-1 in the in-vitro platelet swelling assay. This is perhaps the first report of NHE-1 inhibitory activity of benzotriazole. The 1-alkyl benzotriazole derivatives were found to be more active than the 2-alkyl isomers. The activity increases with increase in chain length of alkyl moiety. Potency increased from that of benzotriazole (IC50= 192.68 μM) to heptyl derivative (compound 13; IC50= 59.23 μM). Introduction of electronegative oxygen atom further increased potency as shown by the benzoyl (compound 16, IC50= 51.57 μM) and sulfonyl groups (compound 17, IC50= 50.89 μM; compound 18, IC50= 49.95 μM).
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, Punjab, India. Electronic address: ddd300@gmail.com.
authors.forename: Dhandeep
authors.initials: D
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, Punjab, India.
authors.forename: Om
authors.initials: O
authors.lastname: Silakari
mesh_terms: D062105:Molecular Docking Simulation; D011487:Protein Conformation; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D017923:Sodium-Hydrogen Exchangers; D014230:Triazoles; C012771:benzotriazole
keywords: Amiloride; Benzotriazole; Platelet swelling assay; Sodium hydrogen exchanger