Choline chloride/urea as a green and efficient deep eutectic solvent in three-component and four-component synthesis of novel pyrazole and pyrano[2,3-c] pyrazole derivatives with antibacterial and antifungal activity

Israa Habeeb Naser; Hassan Thoulfikar A Alamir; Ali Hisham Al-Shukarji; Batool Ali Ahmed; Talal Aziz Qassem; Maher Kamal; Tahani M Almeleebia; Enas R Alwaily; Eftikhaar Hasan Kadhum; Ahmed Alawadi; Ali Alsalamy

doi:10.3389/fchem.2024.1342784

Choline chloride/urea as a green and efficient deep eutectic solvent in three-component and four-component synthesis of novel pyrazole and pyrano[2,3-c] pyrazole derivatives with antibacterial and antifungal activity

Front Chem. 2024 Feb 16:12:1342784. doi: 10.3389/fchem.2024.1342784. eCollection 2024.

Authors

Affiliations

¹ Medical Laboratories Techniques Department, Al-Mustaqbal University, Hillah, Iraq.
² Faculty of Pharmacy, Department of Pharmaceutics, University of Al-Ameed, Karbala, Iraq.
³ Department of Medical Laboratories Technology, Al-Manara College for Medical Sciences, Maysan, Iraq.
⁴ Department of Medical Engineering, Al-Nisour University College, Baghdad, Iraq.
⁵ Department of Medical Laboratory Technics, Al-Noor University College, Nineveh, Iraq.
⁶ Department of Dentistry, Al-Hadi University College, Baghdad, Iraq.
⁷ Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
⁸ Microbiology Research Group, College of Pharmacy, Al-Ayen University, Thi-Qar, Iraq.
⁹ National University of Science and Technology, Dhi Qar, Iraq.
¹⁰ College of Technical Engineering, The Islamic University, Najaf, Iraq.
¹¹ College of Technical Engineering, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq.
¹² College of Technical Engineering, The Islamic University of Babylon, Babylon, Iraq.
¹³ College of Technical Engineering, Imam Ja'afar Al-Sadiq University, Al-Muthanna, Iraq.

Abstract

In this study, choline chloride/urea was used as a green deep eutectic solvent in the three-component reaction of hydrazine/phenylhydrazine, malononitrile, and aromatic aldehydes for synthesizing pyrazole derivatives, and in the four-component reaction of methyl/ethyl acetoacetate, hydrazine/phenylhydrazine, malononitrile, and aromatic aldehydes for synthesizing pyrano[2,3-c]pyrazole derivatives. Elemental analysis, ¹H, and ¹³C NMR spectroscopy were used to confirm the structure of the synthesized pyrazole and pyrano[2,3-c] pyrazole derivatives. The antimicrobial effects of the synthesized pyrazole and pyrano[2,3-c] pyrazole derivatives were investigated. In antimicrobial tests, instructions from clinical and laboratory standards institutes were used. Antimicrobial study was done on pathogenic gram-positive and gram-negative species, and specialized aquatic strains and fungal species. Using choline chloride/urea, novel pyrazole derivatives and pyrano[2,3-c]pyrazole derivatives were synthesized, and other derivatives were synthesized with higher efficiency in less time than some previously reported methods. MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) obtained for derivatives were higher than some antibiotic drugs. Synthesis and reports of new derivatives of pyrazole and pyrano[2,3-c]pyrazole, and investigation and reports of their antimicrobial properties on gram-positive, gram-negative, and specialized aquatic and fungal species are among the novel and important findings of this study.

Keywords: antimicrobial agent; biological evaluation; choline chloride/urea; deep eutectic solvent; pyrano[2,3-c]pyrazole; pyrazole.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University for funding this work through the large research group program under grant number R.G.P.02/535/44.