Synthesis and molecular docking of new indeno[1,2-d]imidazole, indeno[1,2-e]triazine, indeno[1,2-c]pyrazole, and indeno[1,2-b]pyrrole polycyclic compounds as antibacterial and antioxidant agents

Abstract

The present study involves the synthesis of new heterocyclic scaffolds containing indene moiety as indeno[1,2-d]imidazole, indeno[1,2-e]triazine, indeno[1,2-c]pyrazole and indeno[1,2-b]pyrrole compounds. The synthetic strategies are based on the reactions ninhydrin with various nitrogenous nucleophilic reagents (namely: diaryl thioureas, 4-arylthiosemicarbazides, phenylhydrazine / hetarylaldehydes, and enamine reagents). The synthesized fused indenone-based heterocycles are elucidated by considering the data of both elemental and spectral analyses. The antibacterial activities of the synthesized scaffolds were examined against two Gram-positive (B. subtilis and S. aureus) and two Gram-negative (P. aeruginosa and E. coli) bacteria. Among the synthesized heterocycles, 3a, 3b, 8b and 11 exhibited the excellent antibacterial activity against both Gram-positive and Gram-negative bacteria. Evaluation of the synthesized scaffolds revealed a good to excellent antioxidant activities (25.1–87.8 %) using ABTS inhibitory potency. Among these compounds, 3a, 3b, 8b and 11 displayed higher antioxidant activities (83.5–87.8 %) comparing with (Ascorbic acid, 88.0%). The obtained results showed that imidazole, pyrazole and pyrrole ring and methoxy and amide substituents on the phenyl ring increased antioxidant activities of the related heterocycles. Furthermore, the new compounds have been studied theoretically E. coli (PDB ID: 1KZN) and antioxidant enzyme receptor (PDB ID: 3NM8) to investigate their antibacterial and antioxidant activities. Interestingly, the better binding energy provided by the structures 3a-d, 8 and 12 in the silico molecular docking approach reveals its greater affinity for the receptor binding energy.