The fungicidal effectiveness of 2-Chloro-3-hydrazinylquinoxaline, a newly developed quinoxaline derivative, against Candida species

PLoS One. 2024 May 10;19(5):e0303373. doi: 10.1371/journal.pone.0303373. eCollection 2024.

Abstract

Background: Candida represents a prevalent fungal infection, notable for its substantial implications on morbidity and mortality rates. In the landscape of prospective treatments, quinoxaline derivatives emerge as a category of compact compounds exhibiting notable potential in addressing infections. These derivatives showcase promising antimicrobial efficacy coupled with favorable pharmacokinetic and safety characteristics.

Aims: The central aim of this investigation was to examine the antifungal characteristics of 2-Chloro-3-hydrazinylquinoxaline against diverse strains of Candida and Aspergillus in vitro. Additionally, we endeavored to assess the in vivo efficacy of 2-Chloro-3-hydrazinylquinoxaline using a murine model for oral candidiasis induced by C. albicans cells ATCC 10231.

Results: 2-Chloro-3-hydrazinylquinoxaline demonstrated noteworthy effectiveness when tested against various reference strains of Candida species. It exhibited heightened efficacy, particularly against Candida krusei isolates. However, its performance against Candida albicans, Candida tropicalis, Candida glabrata, Candida parapsilosis, and Candida auris isolates exhibited variability. Notably, 2-Chloro-3-hydrazinylquinoxaline manifests variable efficacy against Aspergillus fumigatus, Aspergillus niger, Aspergillus terreus and Aspergillus flavus and no effect against Aspergillus brasiliensis. In a murine model, 2-Chloro-3-hydrazinylquinoxaline exhibited significant efficacy in combating the C. albicans cells ATCC 10231 strain, underscoring its potential as a viable treatment option.

Conclusion: 2-Chloro-3-hydrazinylquinoxaline has demonstrated substantial potential in effectively addressing various Candida and Aspergillus species, showcasing dual attributes of antifungal and anti-inflammatory properties. However, to attain a more comprehensive understanding of its therapeutic capabilities, further investigations, incorporating additional tests and experiments, are imperative.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents* / chemistry
  • Antifungal Agents* / pharmacology
  • Candida* / drug effects
  • Candidiasis / drug therapy
  • Candidiasis / microbiology
  • Disease Models, Animal
  • Female
  • Mice
  • Microbial Sensitivity Tests*
  • Quinoxalines* / chemistry
  • Quinoxalines* / pharmacology

Substances

  • Antifungal Agents
  • Quinoxalines

Grants and funding

Grant number IFPIP:1448-140-1443- 260671 from the Instructional Improvement Fund supported this study. The authors would like to express their appreciation to the Saudi Arabian Moe and King Abdulaziz University, DSR in Jeddah for their technical and financial aid. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Their involvement was solely related to covering the publication fee.