title: Discovery of antitubercular 2,4-diphenyl-1H-imidazoles from chemical library repositioning and rational design.
abstract: TB, caused by Mycobacterium tuberculosis, is one of the deadliest infections worldwide. The co-infection with HIV and the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains have further increased the burden for this disease. In the attempt to respond to the constant need of novel therapeutic options, we herein report the discovery of 2,4-diphenyl-1H-imidazoles as effective antitubercular agents, with MIC in the low micromolar range against actively replicating and persistent M. tuberculosis strains. The good activity, along with the lack of toxicity and the feasible synthesis, underscore their value as novel scaffolds for the development of new anti-TB drugs.
authors.affiliation: Dipartimento di Farmacia, University of Parma, Parco Area delle Scienze 27/A, Parma, 43124, Italy. Electronic address: marco.pieroni@unipr.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Pieroni
authors.affiliation: Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL 60612, USA.
authors.forename: Baojie
authors.initials: B
authors.lastname: Wan
authors.affiliation: Dipartimento di Farmacia, University of Parma, Parco Area delle Scienze 27/A, Parma, 43124, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Zuliani
authors.affiliation: Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL 60612, USA.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Franzblau
authors.affiliation: Dipartimento di Farmacia, University of Parma, Parco Area delle Scienze 27/A, Parma, 43124, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Costantino
authors.affiliation: Dipartimento di Farmacia, University of Parma, Parco Area delle Scienze 27/A, Parma, 43124, Italy. Electronic address: mirko.rivara@unipr.it.
authors.forename: Mirko
authors.initials: M
authors.lastname: Rivara
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D055808:Drug Discovery; D058492:Drug Repositioning; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents
keywords: Drug-repositioning; Imidazoles; Latent tuberculosis; Multidrug-resistance; Tuberculosis