1,2,3-Triazole pharmacophore-based benzofused nitrogen/sulfur heterocycles with potential anti-Moraxella catarrhalis activity

Silvija Maračić; Tatjana Gazivoda Kraljević; Hana Čipčić Paljetak; Mihaela Perić; Mario Matijašić; Donatella Verbanac; Mario Cetina; Silvana Raić-Malić

doi:10.1016/j.bmc.2015.10.042

1,2,3-Triazole pharmacophore-based benzofused nitrogen/sulfur heterocycles with potential anti-Moraxella catarrhalis activity

Bioorg Med Chem. 2015 Dec 1;23(23):7448-63. doi: 10.1016/j.bmc.2015.10.042. Epub 2015 Oct 30.

Authors

Silvija Maračić¹, Tatjana Gazivoda Kraljević¹, Hana Čipčić Paljetak², Mihaela Perić², Mario Matijašić², Donatella Verbanac², Mario Cetina³, Silvana Raić-Malić⁴

Affiliations

¹ Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, HR-10000 Zagreb, Croatia.
² Department for Intercellular Communication, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, Šalata 2, HR-10000 Zagreb, Croatia.
³ Department of Applied Chemistry, Faculty of Textile Technology, University of Zagreb, Prilaz baruna Filipovića 28a, HR-10000 Zagreb, Croatia.
⁴ Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, HR-10000 Zagreb, Croatia. Electronic address: [email protected].

PMID: 26578325
DOI: 10.1016/j.bmc.2015.10.042

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.

Keywords: 1,2,3-Triazole; Antibacterial activity; Coumarin; Fluorescence; Hybridization approach; Moraxella catarrhalis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Azithromycin / pharmacology
Benzothiazoles / chemical synthesis
Benzothiazoles / pharmacology*
Click Chemistry
Heterocyclic Compounds, 2-Ring / chemical synthesis
Heterocyclic Compounds, 2-Ring / chemistry
Heterocyclic Compounds, 2-Ring / pharmacology*
Hydrophobic and Hydrophilic Interactions
Moraxella catarrhalis / drug effects*
Structure-Activity Relationship
Triazoles / chemical synthesis
Triazoles / chemistry
Triazoles / pharmacology*
Umbelliferones / chemical synthesis
Umbelliferones / pharmacology*

Substances

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
Anti-Bacterial Agents
Benzothiazoles
Heterocyclic Compounds, 2-Ring
Triazoles
Umbelliferones
Azithromycin