Pyrrolizine- and Indolizine-Derived Spirooxindoles: Synthesis, Antibacterial Activity and Inverse Docking Analysis

Spirooxindoles are a family of heterocyclic compounds which bear the oxindole nucleus in their structures, which have a considerable pharmaceutical potential and which have been linked to various drugs for the treatment of diverse diseases. In this work, a wide variety of spirooxindoles bearing a pyrrolizinic nucleus were obtained by a 1,3-dipolar cycloaddition reaction between substituted isatins, trans-3-benzoyl acrylic acid and L-proline. In this approach, the target products 9a–m were obtained in 40–86% yields under heating to reflux in methanol over 2 h. Similarly, spirooxindoles containing an indolizinic nucleus 11a–j were obtained in 45–69% yields by switching L-proline for pipecolic acid under heating to reflux in acetonitrile for 8 h. The antibacterial activity of the obtained products was evaluated against P. aeruginosa, K. pneumoniae, E. coli, S. aureus, and N. gonorrhoeae, also including an inverse docking analysis. Results show that 9f and 11i, were the most active compounds against S. aureus, while compounds 9d and 9m displayed the higher activity against N. gonorrhoeae. Inverse docking analysis showed that compounds 9b, 11a 11e, and 11i displayed high affinity to the target protein 6TYM and 7Q6S, which are involved in biological pathways of diverse cancer and Parkinson diseases.