SYNTHESIS OF NOVEL 1-(3-PHENYLBENZO[C]ISOXAZOL-5-YL)-1H-1,2,3-TRIAZOLE-4-CARBOXAMIDES AND THEIR ANTIBACTERIAL AND ANTIFUNGAL ACTIVITIES

Nazariy T.  Pokhodylo; Mykola A.  Tupychak; Orest O.  Bonetskyi; Nadiia M.  Grynchyshyn; Vasyl S.  Matiychuk

doi:10.15421/jchemtech.v32i2.297699

Authors

Nazariy T. Pokhodylo Ivan Franko National University of Lviv, Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies, Ukraine https://orcid.org/0000-0001-8222-5008
Mykola A. Tupychak Ivan Franko National University of Lviv, Ukraine https://orcid.org/0000-0002-9880-0983
Orest O. Bonetskyi Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies, Ukraine
Nadiia M. Grynchyshyn Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies, Ukraine https://orcid.org/0000-0003-1627-0120
Vasyl S. Matiychuk Ivan Franko Lviv National University, Ukraine https://orcid.org/0000-0001-8077-2139

DOI:

https://doi.org/10.15421/jchemtech.v32i2.297699

Keywords:

azide; benzo[c]isoxazoles; 1H-1,2,3-triazole-4-carboxamides; antimicrobial.

Abstract

Novel 1-(3-arylbenzo[c]isoxazol-5-yl)-1H-1,2,3-triazole-4-carboxamides were designed, synthesizing and evaluated for antimicrobial activity toward five key ESKAPE pathogenic bacteria, one Gram‐positive bacteria methicillin‐resistant Staphylococcus aureus (ATCC 43300), four Gram‐negative bacteria, Escherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 700603), Acinetobacter baumannii (ATCC 19606), and Pseudomonas aeruginosa (ATCC 27853) and antifungal activity towards two pathogenic fungal strains Candida albicans (ATCC 90028) and Cryptococcus neoformans var. Grubii (H99; ATCC 208821). The target compounds were obtained in a convenient synthetic path including consequent Dimroth cyclocondensation of 4-nitrophenyl azide with β-ketoesters, vicarious nucleophilic substitution in nitroaryl fragments and amidation of 1,2,3-triazole-4-carboxylic acid motif. In this way, a mini combinatorial library of 24 compounds was obtained with good overall yields. Five compounds, 7a, 7b, 7i, 7t and 7u, reduced the growth of microorganisms by approximately 20 %. Compounds 7b, 7i, and 7u demonstrated the inhibitory activity towards Staphylococcus aureus. In contrary 7a and 7t towards Cryptococcus neoformans. The data obtained will be used for further design and scaffold optimization.

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SYNTHESIS OF NOVEL 1-(3-PHENYLBENZO[C]ISOXAZOL-5-YL)-1H-1,2,3-TRIAZOLE-4-CARBOXAMIDES AND THEIR ANTIBACTERIAL AND ANTIFUNGAL ACTIVITIES

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