title: Design, synthesis and evaluation of novel polypharmacological antichlamydial agents.
abstract: Discovery of new polypharmacological antibacterial agents with multiple modes of actions can be an alternative to combination therapy and also a possibility to slow development of antibiotic resistance. In support to this hypothesis, we synthesized 16 compounds by combining the pharmacophores of Chlamydia trachomatis inhibitors and inhibitors of type III secretion (T3S) in gram-negative bacteria. In this study we have developed salicylidene acylhydrazide sulfonamides (11c &11d) as new antichlamydial agents that also inhibit T3S in Yersinia pseudotuberculosis.
authors.affiliation: Department of Chemistry, Umeå University, SE90187 Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), SE90187 Umeå, Sweden.
authors.forename: Naresh
authors.initials: N
authors.lastname: Sunduru
authors.affiliation: Department of Chemistry, Umeå University, SE90187 Umeå, Sweden; Department of Clinical Microbiology, Umeå University, SE90187 Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), SE90187 Umeå, Sweden.
authors.forename: Olli
authors.initials: O
authors.lastname: Salin
authors.affiliation: Department of Chemistry, Umeå University, SE90187 Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), SE90187 Umeå, Sweden; Molecular Infection Medicine Sweden (MIMS), Umeå University, SE90187 Umeå, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Gylfe
authors.affiliation: Department of Chemistry, Umeå University, SE90187 Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), SE90187 Umeå, Sweden. Electronic address: mikael.elofsson@chem.umu.se.
authors.forename: Mikael
authors.initials: M
authors.lastname: Elofsson
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D064798:Polypharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015011:Yersinia pseudotuberculosis / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D006834:Hydrazines; D013449:Sulfonamides
keywords: Acylhydrazones; Antibiotic development; Chlamydia pneumoniae; Chlamydia trachomatis; Cyanation; Heck coupling; Sulfonamides; Thiourea derivatives; Type III secretion system; Urea derivatives