title: Benzotriazoles and indazoles are scaffolds with biological activity against Entamoeba histolytica.
abstract: Parasitic infections caused by Entamoeba histolytica are still major threats against public health, especially in developing countries. Although current therapies exist, the problems associated with parasite resistance and negative side effects make it imperative to search for new therapeutic agents. A systematic scaffold analysis reported herein of a public database containing 474 antiamoebic compounds reveals that benzimidazole is the most active scaffold reported thus far. To gain insights into the antiamoebic activity of novel compounds, the authors report herein the biological activity of 12 compounds, including benzotriazole and indazole derivatives, scaffolds not previously tested against E. histolytica. Compounds with the benzotriazole and indazole scaffolds showed low micromolar activity (IC(50) = 0.304 and 0.339 µM) and are more active than metronidazole, which is the drug of choice used for the treatment of amebiosis. The novel compounds have similar properties to approved drugs. Compounds with novel scaffolds represent promising starting points of an optimization program against E. histolytica.
authors.affiliation: Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA. fvallejo@tpims.org
authors.forename: Fabian
authors.initials: F
authors.lastname: López-Vallejo
authors.forename: Rafael
authors.initials: R
authors.lastname: Castillo
authors.forename: Lilián
authors.initials: L
authors.lastname: Yépez-Mulia
authors.forename: José L
authors.initials: JL
authors.lastname: Medina-Franco
mesh_terms: D000563:Amebicides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016208:Databases, Factual; D004748:Entamoeba histolytica / Q000187:drug effects* / Q000254:growth & development; D004749:Entamoebiasis / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007191:Indazoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D008795:Metronidazole / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D021281:Quantitative Structure-Activity Relationship; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000563:Amebicides; D001562:Benzimidazoles; D007191:Indazoles; D054852:Small Molecule Libraries; D014230:Triazoles; D008795:Metronidazole; C012771:benzotriazole