Eco-conscious synthesis of novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives as potent Anti-microbial agent and comparative study of cell viability and cytotoxicity in HEK-293 cell line utilizingIndian gooseberry (Phyllanthus emblica) fruit extract

Bioorg Chem. 2024 Dec:153:107936. doi: 10.1016/j.bioorg.2024.107936. Epub 2024 Nov 6.

Abstract

Antimicrobial resistance (AMR) is a pressing global health challenge that necessitates the search for novel antimicrobial agents and synthetic methodologies. This study investigates the synthesis and antimicrobial efficacy of 25 novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives, catalyzed by Amla (Phyllanthus emblica) fruit juice, which is rich in organic acids and polyphenolic compounds, thus serving as an environmentally sustainable catalyst, in adherence to green chemistry principles. The synthesis is achieved through a one-pot, solvent-free process that yields high quantities of the desired compounds in significantly less time compared to traditional methods. Comprehensive antimicrobial evaluation was conducted against a range of clinically relevant microorganisms, including Chromobacterium violaceum, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Cryptococcus neoformans and Aspergillus niger. Concurrently, cytotoxic assays were performed on HEK-293 cells, to assess safety profiles, revealing that compounds B-1, B-6, B-7, B-14 and B-15 exhibited potent antimicrobial activity while maintaining low cytotoxicity and high cell viability. These findings underscore the therapeutic potential of the synthesized compounds in combatting infectious diseases and addressing the challenges posed by AMR, highlighting the critical importance of dose optimization in therapeutic applications. This study combats contagious diseases, mitigates AMR challenges and contributes significantly to the field of antimicrobial drug discovery, emphasizing the need for sustainable synthetic strategies that align with future pharmaceutical endeavors. Our research not only advances the understanding of these novel compounds but also supports ongoing efforts to develop safe and effective therapies against resistant pathogens.

Keywords: 1,2,4-triazolo[1,5-a]pyrimidine; Amla (Phyllanthus emblica) fruit extract; Antimicrobial drug discovery; Challenging conventional paradigms; Innovative synthetic methodologies.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Bacterial Agents* / chemical synthesis
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology
  • Cell Survival* / drug effects
  • Dose-Response Relationship, Drug
  • Fruit / chemistry
  • HEK293 Cells
  • Humans
  • Microbial Sensitivity Tests*
  • Molecular Structure
  • Phyllanthus emblica / chemistry
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Pyrimidines* / chemical synthesis
  • Pyrimidines* / chemistry
  • Pyrimidines* / pharmacology
  • Structure-Activity Relationship
  • Triazoles* / chemical synthesis
  • Triazoles* / chemistry
  • Triazoles* / pharmacology

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Plant Extracts
  • Pyrimidines
  • Triazoles
  • 1,2,4-triazolo(1,5-a)pyrimidine