Green multicomponent synthesis, antimicrobial and antioxidant evaluation of novel 5-amino-isoxazole-4-carbonitriles

Abstract

Background

Design and synthesis of new inhibitor agents to deal with pathogenic microorganisms is expanding. In this project, an efficient, environmentally friendly, economical, rapid and mild procedure was developed for the synthesis of novel functionalized isoxazole derivatives as antimicrobial potentials.

Methods

Multicomponent reaction between malononitrile ( 1), hydroxylamine hydrochloride ( 2) and different aryl or heteroaryl aldehydes 3a– i afforded novel 5-amino-isoxazole-4-carbonitriles 4a– i in good product yields and short reaction times. Deep eutectic solvent K ₂CO ₃/glycerol was used as catalytic reaction media. Structure of all molecules were characterized by different analytical tools. In vitro inhibitory activity of all derivatives was evaluated against a variety of pathogenic bacteria including both Gram-negative and Gram-positive strains as well as some fungi. In addition, their free radical scavenging activities were assessed against DPPH.

Results

Broad-spectrum antimicrobial activities were observed with isoxazoles 4a, b, d. In addition, antioxidant activity of isoxazole 4i was proven on DPPH.

Conclusions

In this project, compounds 4a, b, d could efficiently inhibit the growth of various bacterial and fungal pathogens. Antioxidant properties of derivative 4i were also significant. These biologically active compounds are suitable candidates to synthesize new prodrugs and drugs due to the presence of different functional groups on their rings.

Electronic supplementary material

The online version of this article (10.1186/s13065-018-0488-0) contains supplementary material, which is available to authorized users.