New marine-derived indolymethyl pyrazinoquinazoline alkaloids with promising antimicrobial profiles. Issue 52 (21st August 2020)

• Record Type: Journal Article
• Authors: Long, Solida; Resende, Diana I. S. P.; Palmeira, Andreia; Kijjoa, Anake; Silva, Artur M. S.; Tiritan, Maria Elizabeth; Pereira-Terra, Patrícia; Freitas-Silva, Joana; Barreiro, Sandra; Silva, Renata; Remião, Fernando; Pinto, Eugénia; Martins da Costa, Paulo; Sousa, Emília; Pinto, Madalena M. M.
• Is Part Of: RSC advances. Volume 10:Issue 52(2020)
• Page Start: 31187
• Page End: 31204
• Publication Date: 2020-08-21
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d0ra05319h
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Indolomethyl pyrazino [1, 2- b ]quinazoline-3, 6-diones were prepared using a one-pot multicomponent polycondensation of amino acids and were evaluated for their antimicrobial activity against a panel of nine bacterial strains and five fungal strains. 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.