New marine-derived indolymethyl pyrazinoquinazoline alkaloids with promising antimicrobial profiles

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.

Determination of the Absolute Configuration of Bioactive Indole-Containing Pyrazino[2,1-b]quinazoline-3,6-diones and Study of Their In Vitro Metabolic Profile

“…Owing to the increasing interest of fiscalin B ( 1 ) in medicinal and organic chemistry, some synthetic procedures enabling its facile production have been developed in recent decades [ 6 , 8 , 9 , 17 ]. Recently, we reported the synthesis and biological activities of four different series of indole-containing pyrazino[2,1- b ]quinazoline-3,6-diones by using this synthetic methodology as well as by performing different modifications in order to study the structure–activity relationship [ 14 , 15 , 16 , 18 ]. From these studies, we were able to obtain a significant number of hit compounds, either as neuroprotective, antitumor, and antibacterial agents [ 14 , 15 , 16 , 18 ].…”

“…Recently, we reported the synthesis and biological activities of four different series of indole-containing pyrazino[2,1- b ]quinazoline-3,6-diones by using this synthetic methodology as well as by performing different modifications in order to study the structure–activity relationship [ 14 , 15 , 16 , 18 ]. From these studies, we were able to obtain a significant number of hit compounds, either as neuroprotective, antitumor, and antibacterial agents [ 14 , 15 , 16 , 18 ]. Herein, we report the concise total synthesis of 1 , possessing antimalarial activity [ 16 ], and its derivative 4-[(1 H -indol-3-yl)methyl]-8,10-dichloro-1-isobutyl-1,2-dihydro-6 H -pyrazino[2,1- b ]quinazoline-3,6(4 H )-dione 2 , a hit compound with antibacterial activity [ 18 ], in gram scale via a microwave-assisted methodology.…”

“…From these studies, we were able to obtain a significant number of hit compounds, either as neuroprotective, antitumor, and antibacterial agents [ 14 , 15 , 16 , 18 ]. Herein, we report the concise total synthesis of 1 , possessing antimalarial activity [ 16 ], and its derivative 4-[(1 H -indol-3-yl)methyl]-8,10-dichloro-1-isobutyl-1,2-dihydro-6 H -pyrazino[2,1- b ]quinazoline-3,6(4 H )-dione 2 , a hit compound with antibacterial activity [ 18 ], in gram scale via a microwave-assisted methodology. This derivative exhibited potent antibacterial activity against S. aureus strains, with MIC values of 4 µg/mL for a reference strain ( S. aureus ATCC 29213, positive control cefotaxime MIC = 8 µg/mL) and 8 µg/mL for a methicillin-resistant strain ( S. aureus 66/1, positive control kanamycin MIC = 32 µg/mL).…”

“…This derivative exhibited potent antibacterial activity against S. aureus strains, with MIC values of 4 µg/mL for a reference strain ( S. aureus ATCC 29213, positive control cefotaxime MIC = 8 µg/mL) and 8 µg/mL for a methicillin-resistant strain ( S. aureus 66/1, positive control kanamycin MIC = 32 µg/mL). Compared with the structurally related marine natural product neofiscalin A [ 19 ], a two-fold reduction in the MIC values was observed, showing that simpler molecules are quite promising to find new agents to overcome multidrug-resistant (MDR) strains [ 18 ]. Furthermore, 2 was able to impair S. aureus biofilm production, and no significant cytotoxicity towards differentiated and non-differentiated SH-SY5Y cells was observed [ 18 ].…”

“…Compared with the structurally related marine natural product neofiscalin A [ 19 ], a two-fold reduction in the MIC values was observed, showing that simpler molecules are quite promising to find new agents to overcome multidrug-resistant (MDR) strains [ 18 ]. Furthermore, 2 was able to impair S. aureus biofilm production, and no significant cytotoxicity towards differentiated and non-differentiated SH-SY5Y cells was observed [ 18 ].…”