title: 1,2,3-Triazole pharmacophore-based benzofused nitrogen/sulfur heterocycles with potential anti-Moraxella catarrhalis activity.
abstract: Versatile 1,2,3-triazole pharmacophore-based benzofused heterocycles containing halogen-substituted aromatic (9-17 and 25-28), 7-substituted coumarin (18-23 and 29-30) or penciclovir-like subunit (31a,b-38a) were designed and synthesized to evaluate their antibacterial activities against selected Gram-positive and Gram-negative bacteria. Hybridization approach using environmentally friendly Cu(I)-catalyzed click reaction under microwave irradiation was adopted in the synthesis of regioselective 1,4-disubstituted 1,2,3-triazole tethered heterocycles (9-23 and 25-30), while post-N-alkylation of NH-1,2,3-triazoles afforded both 2,4- (31a-38a) and 1,4-disubstituted (31b-33b, 35b-37b) 1,2,3-triazole regioisomers. The compounds 18-23 and 25-30 revealed fluorescence in the violet region of the visible spectrum with a strong influence of phenyl spacer in 25-30 on both wavelength and emission intensity. Fusion of selected subunits led to new hybrid architecture, benzothiazole-1,2,3-triazole-coumarin 29 that demonstrated extremely narrow spectrum activity towards fastidious Gram-negative bacteria Moraxella catarrhalis. Selected hybrid showed the potency against Moraxella catarrhalis (MIC⩽0.25μg/mL) comparable to that of reference antibiotic azithromycin, which suggested that further investigations are necessary to optimize this potential hit compound as a new anti-Moraxella catarrhalis agent.
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, HR-10000 Zagreb, Croatia.
authors.forename: Silvija
authors.initials: S
authors.lastname: Maračić
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, HR-10000 Zagreb, Croatia.
authors.forename: Tatjana Gazivoda
authors.initials: TG
authors.lastname: Kraljević
authors.affiliation: Department for Intercellular Communication, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, Šalata 2, HR-10000 Zagreb, Croatia.
authors.forename: Hana Čipčić
authors.initials: HČ
authors.lastname: Paljetak
authors.affiliation: Department for Intercellular Communication, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, Šalata 2, HR-10000 Zagreb, Croatia.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Perić
authors.affiliation: Department for Intercellular Communication, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, Šalata 2, HR-10000 Zagreb, Croatia.
authors.forename: Mario
authors.initials: M
authors.lastname: Matijašić
authors.affiliation: Department for Intercellular Communication, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, Šalata 2, HR-10000 Zagreb, Croatia.
authors.forename: Donatella
authors.initials: D
authors.lastname: Verbanac
authors.affiliation: Department of Applied Chemistry, Faculty of Textile Technology, University of Zagreb, Prilaz baruna Filipovića 28a, HR-10000 Zagreb, Croatia.
authors.forename: Mario
authors.initials: M
authors.lastname: Cetina
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, HR-10000 Zagreb, Croatia. Electronic address: sraic@fkit.hr.
authors.forename: Silvana
authors.initials: S
authors.lastname: Raić-Malić
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D057930:Click Chemistry; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D001936:Moraxella catarrhalis / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014468:Umbelliferones / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: C000610532:4-((4-((4-(6-methylbenzo(d)thiazol-2-yl)phenylamino)methyl)-1H-1,2,3-triazol-1-yl)methyl)-7-hydroxy-4a,8a-dihydro-2H-chromen-2-one; D000900:Anti-Bacterial Agents; D052160:Benzothiazoles; D006574:Heterocyclic Compounds, 2-Ring; D014230:Triazoles; D014468:Umbelliferones; D017963:Azithromycin
keywords: 1,2,3-Triazole; Antibacterial activity; Coumarin; Fluorescence; Hybridization approach; Moraxella catarrhalis