New marine-derived indolymethyl pyrazinoquinazoline alkaloids with promising antimicrobial profiles

Abstract

Due to the emergence of multidrug-resistant pathogenic microorganisms, the search for novel antimicrobials is urgent. Inspired by marine alkaloids, a series of indolomethyl pyrazino [1,2-b]quinazoline-3,6-diones was prepared using a one-pot microwave-assisted multicomponent polycondensation of amino acids. The compounds were evaluated for their antimicrobial activity against a panel of nine bacterial strains and five fungal strains. Compounds 26 and 27 were the most effective against Staphylococcus aureus ATCC 29213 reference strain with MIC values of 4 μg mL⁻¹, and a methicillin-resistant Staphylococcus aureus (MRSA) isolate with MIC values of 8 μg mL⁻¹. It was possible to infer that enantiomer (−)-26 was responsible for the antibacterial activity (MIC 4 μg mL⁻¹) while (+)-26 had no activity. Furthermore, compound (−)-26 was able to impair S. aureus biofilm production and no significant cytotoxicity towards differentiated and non-differentiated SH-SY5Y cells was observed. Compounds 26, 28, and 29 showed a weak antifungal activity against Trichophyton rubrum clinical isolate with MIC 128 μg mL⁻¹ and presented a synergistic effect with fluconazole.