Indene and indole-based compounds as potential antimicrobial agents: synthesis, activity, docking studies and ADME
Vilma Lovrinčević1, Monika Šabić Runjavec2, Nikica Baričević1
1Department of Organic Chemistry, University of Zagreb Faculty of Chemical Engineering and Technology Trg Marka Marulića 19 HR-10000 Zagreb Croatia dvuk@fkit.unizg.hr.
RSC Advances
|February 25, 2026
Summary
New indole and indene derivatives show promise in combating antibiotic resistance. These compounds exhibit antibacterial and antifungal activity, with potential interactions with key bacterial and fungal enzymes.
Area of Science:
- Medicinal Chemistry
- Antimicrobial Drug Discovery
- Organic Synthesis
Background:
- Antibiotic resistance is a growing global health crisis, necessitating the development of novel antimicrobial agents.
- Existing antibiotic classes are becoming less effective due to accelerated bacterial resistance.
- Structurally diverse compounds are crucial for overcoming resistance mechanisms.
Purpose of the Study:
- To synthesize and characterize novel indole and indene derivatives.
- To evaluate the antibacterial and antifungal activities of these synthesized compounds.
- To investigate the molecular mechanisms underlying their antimicrobial potential.
Main Methods:
- Synthesis and characterization of various indole and indene derivatives.
- In vitro testing of antibacterial activity against *Bacillus subtilis* and *Pseudomonas aeruginosa*.
- In vitro testing of antifungal activity against *Candida lipolytica* and *Aspergillus niger*.
- Molecular docking studies targeting DNA gyrase B (GyrB) and 14α-sterol demethylase (CYP51).
- *In silico* ADME (Absorption, Distribution, Metabolism, and Excretion) predictions.
Main Results:
- Most synthesized compounds demonstrated antifungal activity and antibacterial activity against *Bacillus subtilis*.
- All tested compounds were inactive against *Pseudomonas aeruginosa*.
- Pyrrole, pyridine, and phenol derivatives exhibited significant antibacterial and antifungal properties.
- Molecular docking revealed strong binding interactions with GyrB and CYP51 for promising derivatives.
- *In silico* ADME predictions suggested favorable physicochemical properties.
Conclusions:
- Novel indole and indene derivatives possess significant antimicrobial potential, particularly against Gram-positive bacteria and fungi.
- The identified compounds, especially pyrrole, pyridine, and phenol derivatives, warrant further investigation as lead compounds for new antibiotic development.
- Binding interactions with GyrB and CYP51 provide a mechanistic basis for the observed antimicrobial activities, guiding future drug design.
