Synthesis, Spectral Characterization, and Biological Evaluation of Novel [1,2,4]Triazolo[3,4-a]isoquinolines and 5,6-Dihydropyrrolo[2,1-a]isoquinolines: Insights From Molecular Docking, ADMET, and Antibacterial Studies

This study discussed the synthesis of novel [1,2,4]triazolo[3,4-a]isoquinolines and 5,6-dihydropyrrolo[2,1-a]isoquinolines as promising antibacterial agents, showing the significance of isoquinoline scaffold to enhance these biological activities. [1,2,4]Triazolo[3,4-a]isoquinolines 6-8 and 5,6-dihydropyrrolo[2,1-a]isoquinolines 9, 10 were obtained by the reaction of hydrazonoyl chlorides 3-5 with 6,7-dimethoxy-3,4-dihydroisoquinolines 1a,b and ethyl 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)acetate 2, respectively, in chloroform in the presence of triethylamine. Utility of [1,2,4]triazolo[3,4-a]isoquinolines 6a in the synthesis of enamoinone 11, [1,2,4]triazolo[3,4-a]isoquinolin-pyrazoles 13a-e, and chalcones 21a-g. Following structural confirmation via spectral data, the newly synthesized compounds were evaluated for antibacterial efficacy against two Gram-positive and two Gram-negative bacterial strains. The findings revealed that compounds 6a and 8a exhibited significant antibacterial activity against Salmonella, with inhibition zones measuring 23 and 18 mm, respectively. In contrast, compounds 7a and 13e demonstrated notable activity against E. coli, showing inhibition zones of 13 and 27 mm, respectively, while compound 13d was effective against Listeria monocytogenes with a 12 mm inhibition zone. The remaining compounds displayed no observable antibacterial properties. Molecular docking simulations were performed for the most active compounds, 13d and 13e, supporting their potential as promising inhibitors. Compound 13e was identified as a potential inhibitor of E. coli DNA gyrase subunit B (P0AES6), while compound 13d showed inhibitory potential against transglycosylases of L. monocytogenes (A0A0E1R719).