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

Publication date: Available online 30 October 2015
Source:Bioorganic & Medicinal Chemistry
Author(s): Silvija Maračić, Tatjana Gazivoda Kraljević, Hana Čipčić Paljetak, Mihaela Perić, Mario Matijašić, Donatella Verbanac, Mario Cetina, Silvana Raić-Malić
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 environmetally 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 extremly narrow spectrum activity towards fastidious Gram-negative bacteria M. catarrhalis. Selected hybrid showed the potency against Moraxella catarrhalis (MIC ⩽ 0.25 μg/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.

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