Indene and indole-based compounds as potential antimicrobial agents: synthesis, activity, docking studies and ADME analysis

Abstract

The excessive use of antibiotics in recent years has led to an accelerated development of resistance in bacterial pathogens and thus to one of the greatest problems of our time: antibiotic resistance. Therefore, despite the large number of available drugs, the development of new and structurally diverse antibiotics is urgently needed. In this study, various indole and indene derivatives were prepared and characterised and their antibacterial activity against Gram-positive bacteria Bacillus subtilis 3020 and Gram-negative bacteria Pseudomonas aeruginosa 3011 was investigated. Two fungal strains, Candida lipolytica 59 and Aspergillus niger 405, were used for antifungal activity. In general, most of the prepared compounds showed potential antifungal activity and antibacterial activity against Bacillus subtilis 3020, while all compounds were inactive against Pseudomonas aeruginosa 3011. The most promising compounds were pyrrole, pyridine and phenol derivatives, which showed antibacterial and antifungal activity. In addition, molecular docking studies showed that the most promising indole and indene derivatives exhibited significant binding interaction networks and binding affinity with DNA gyrase B (GyrB) and 14α-sterol demethylase (CYP51), consistent with their observed antibacterial and antifungal activities. Finally, in silico ADME predictions indicated acceptable physicochemical properties of the newly designed compounds.