New Mono- and Bis-Sulfonyl Succinimides Bearing 1,2,3,4-Tetrahydroisoquinoline/p-Toluene Moiety: Efficient Synthesis, Computational Study, and Antimicrobial Activity

Abstract

Several mono-succinimides with a sulfonyl moiety, as well as the bis-succinimide derivatives, were generated using ultrasound. In the presence of an environmentally friendly boric acid (H3BO3), some substituted maleimides and different amines are used in this synthetic method. Synthesized derivatives were obtained with good chemical yields (up to 92%) and identified using 1H, 13C NMR, and MS analytical data. The antimicrobial efficacy of the produced compounds was assessed at varying concentrations against three gram-negative bacteria (E. coli, P. aeruginosa, and K. pneumoniae), one gram-positive bacterium (S. aureus), and one fungal strain (C. albicans). The results showed that some molecules successfully inhibited all the tested microorganisms. According to molecular docking simulations, the new mono- and bis-succinimide derivatives demonstrated a high docking score, good stability, and favorable intermolecular interactions in the pocket of Staphylococcus aureus tyrosyl-tRNA synthetase (TyrRS) in comparison to the native PDB ligand (SB-239629) and the reference drug ciprofloxacin (CIP). DMol3/DFT calculations at the BLYP method show that the ligands under study are reactive and unstable based on values for EHOMO, ELUMO, and ΔEgap. Furthermore, the ADME/T analyses demonstrate that every synthesized molecule had good bioavailability and pharmacokinetics. Overall, the in vitro and in silico results demonstrate the compounds’ promising antimicrobial qualities.