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

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 synthe-sized 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 activ-ities (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 anti-oxidant 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.

Automated summary

This study synthesized a series of heterocyclic compounds containing an indene moiety, including indeno[1,2-d]imidazole, indeno[1,2-e]triazine, indeno[1,2-c]pyrazole, and indeno[1,2-b]pyrrole. The synthesis strategy involved reactions of ninhydrin with various nitrogenous nucleophilic reagents. The synthesized compounds showed excellent antibacterial activity against both Gram-positive and Gram-negative bacteria. They also exhibited good to excellent antioxidant activity. The compounds with imidazole, pyrazole, and pyrrole rings, as well as methoxy and amide substituents, showed enhanced antioxidant activity.