Two Step One-Pot Synthesis of 7-Azaindole Linked 1,2,3-Triazole Hybrids: In-Vitro and In-Silico Antimicrobial Evaluation

ChemMedChem. 2024 Dec 16;19(24):e202400451. doi: 10.1002/cmdc.202400451. Epub 2024 Oct 22.

Abstract

Herein, we report design, synthesis and characterization of a new library of 7-azaindole N-ethyl linked 1,2,3-triazoles containing ethylene as a spacer unit, and evaluation of all the synthesized compounds for their antimicrobial properties. Antibacterial potential was checked against two Gram positive (B. subtilis and S. aureus) and two Gram negative (E. coli and P. aeruginosa) bacterial strains while antifungal potential was assayed against two fungal strains (C. albicans and A. niger). All the tested compounds showed satisfactory antibacterial potency in comparison to reference drug ciprofloxacin with MIC values ranging from 0.0108 to 0.0432 μmol/mL. Interestingly, except two, all the target compounds showed better antifungal property as compared to the reference drug fluconazole with MIC values less than 0.0408 μmol/mL. One of the compounds exhibited two-fold better antifungal potential in comparison to fluconazole. Furthermore, in-silico ADMET and DFT studies reported drug likeness behavior and chemical reactivity parameters, respectively. The cytotoxicity results on substrate azide 3 and most potent 1,2,3-triazoles (5 d and 5 l) were found to be non-toxic.

Keywords: 1,2,3-Triazole; 7-Azaindole; ADMET; Antimicrobial study; Cytotoxicity; Molecular docking.

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
  • Aspergillus niger / drug effects
  • Candida albicans* / drug effects
  • Density Functional Theory
  • Dose-Response Relationship, Drug
  • Gram-Positive Bacteria / drug effects
  • Humans
  • Indoles* / chemical synthesis
  • Indoles* / chemistry
  • Indoles* / pharmacology
  • Microbial Sensitivity Tests*
  • Molecular Structure
  • Pseudomonas aeruginosa / drug effects
  • Structure-Activity Relationship
  • Triazoles* / chemical synthesis
  • Triazoles* / chemistry
  • Triazoles* / pharmacology

Substances

  • Triazoles
  • Antifungal Agents
  • Anti-Bacterial Agents
  • Indoles
  • 7-azaindole dimer

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