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
LQOF - Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto Rua de Jorge Viterbo Ferreira, 228 4050-313 Porto Portugal
CIIMAR - Centro Interdisciplinar de Investigação Marinha e Ambiental, Terminal de Cruzeiros do Porto de Leixões Av. General Norton de Matos S/N 4450-208 Matosinhos Portugal.
RSC Adv. 2020 Aug 21;10(52):31187-31204. doi: 10.1039/d0ra05319h.
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-]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 ATCC 29213 reference strain with MIC values of 4 μg mL, and a methicillin-resistant (MRSA) isolate with MIC values of 8 μg mL. It was possible to infer that enantiomer (-)-26 was responsible for the antibacterial activity (MIC 4 μg mL) while (+)-26 had no activity. Furthermore, compound (-)-26 was able to impair 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 clinical isolate with MIC 128 μg mL and presented a synergistic effect with fluconazole.
由于多重耐药致病微生物的出现，寻找新型抗菌药物迫在眉睫。受海洋生物碱的启发，通过氨基酸的一锅法微波辅助多组分缩聚反应制备了一系列吲哚甲基吡嗪并[1,2 -]喹唑啉 - 3,6 - 二酮。评估了这些化合物对一组九种细菌菌株和五种真菌菌株的抗菌活性。化合物26和27对ATCC 29213参考菌株最有效，MIC值为4μg/mL；对耐甲氧西林金黄色葡萄球菌（MRSA）分离株的MIC值为8μg/mL。可以推断对映体（-）-26具有抗菌活性（MIC为4μg/mL），而（+）-26无活性。此外，化合物（-）-26能够抑制生物膜形成，并且未观察到对分化和未分化的SH - SY5Y细胞有明显的细胞毒性。化合物26、28和29对临床分离株显示出较弱的抗真菌活性，MIC为128μg/mL，并与氟康唑呈现协同作用。
