Microwave-assisted preparation and antimicrobial activity of O-alkylamino benzofurancarboxylates

Abstract

A series of derivatives of 2 and 3-benzofurancarboxylates were synthesized under microwave-assisted conditions. Their in-vitro antimicrobial properties were assessed. Inhibition by the compounds of the growth of antibiotic-susceptible standards and clinically isolated strains of Gram-positive and Gram-negative bacteria, yeasts, and a human fungal pathogen was moderate to significant. Methyl 5-bromo-7-[2-(N,N-diethylamino)ethoxy]-6-methoxy-2-benzofurancarboxylate hydrochloride was identified as the most active compound (MIC 3–12 × 10−3 μmol/cm3 against Gram-positive bacteria; MIC 9.4 × 10−2 μmol/cm3 against Candida and Aspergillus brasiliensis). The molecular and crystal structures of 2-(N,N-diethylamino)ethyl 6-acetyl-5-hydroxy-2-methyl-3-benzofurancarboxylate were established by single-crystal X-ray diffraction.Graphical Abstract.

Synthesis and Biological Studies of Benzo[b]furan Derivatives: A Review from 2011 to 2022

“…In a subsequent study conducted in 2013, Ostrowska et al synthesized a series of chlorinated 2- and 3-benzo[ b ]furan carboxylates ( Scheme 21 and Table 34 ). These derivatives underwent meticulous in vitro assessments to gauge their antimicrobial efficacy against both bacterial strains, as previously discussed, and fungal strains [ 60 , 61 ]. In terms of antifungal activity, they were scrutinized across strains encompassing Aspergillus brasiliensis , Candida albicans, Candida parapsilosis, Saccharomyces cerevisiae , and Zygosaccharomyces rouxii .…”

“…This adaptability is apparent in the various structural modifications involving the incorporation of different functional groups at the six carbons of the structure ( Figure 56 ). Beginning with the former, significant activity was observed against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) [ 58 , 64 , 65 ], Staphylococcus aureus Newman [ 64 ], Staphylococcus aureus [ 59 , 61 ], Bacillus subtilis [ 59 , 61 , 62 ], Micrococcus luteus [ 61 ], Bacillus cereus [ 61 ], Staphylococcus epidermidis [ 61 ], Enterococcus hirae [ 61 ], vancomycin-sensitive Enterococcus faecalis (VSE) [ 65 ], vancomycin-resistant Enterococcus faecalis (VRE) [ 65 ], and vancomycin-resistant Enterococcus faecium (VRE). Additionally, Gram-negative bacteria were targeted, including Escherichia coli [ 59 , 61 , 62 ], Pseudomonas aeruginosa [ 59 , 61 ], Pseudomonas syringae [ 62 ], Salmonella typhi [ 62 ], and Klebsiella pneumoniae [ 62 ].…”

“…Beginning with the former, significant activity was observed against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) [ 58 , 64 , 65 ], Staphylococcus aureus Newman [ 64 ], Staphylococcus aureus [ 59 , 61 ], Bacillus subtilis [ 59 , 61 , 62 ], Micrococcus luteus [ 61 ], Bacillus cereus [ 61 ], Staphylococcus epidermidis [ 61 ], Enterococcus hirae [ 61 ], vancomycin-sensitive Enterococcus faecalis (VSE) [ 65 ], vancomycin-resistant Enterococcus faecalis (VRE) [ 65 ], and vancomycin-resistant Enterococcus faecium (VRE). Additionally, Gram-negative bacteria were targeted, including Escherichia coli [ 59 , 61 , 62 ], Pseudomonas aeruginosa [ 59 , 61 ], Pseudomonas syringae [ 62 ], Salmonella typhi [ 62 ], and Klebsiella pneumoniae [ 62 ]. Furthermore, enzymatic assays were performed against typical Staphylococcus aureus enzymes, specifically 4,4′-diapophytoene desaturase (CrtN) [ 64 ] and cysteine transpeptidase Sortase A (SrtA) [ 66 ].…”

“…This review reveals that at a structural level, numerous benzo[ b ]furan derivatives exhibit both antibacterial and antifungal properties, as illustrated in Figure 56 . The fungal strains examined within the studies discussed in this review displayed significant efficacy against Candida albicans ( C. albicans ) [ 58 , 61 ], Candida neoformans ( C. neoformans ) [ 58 ], Candida parapsilosis ( C. parapsilosis ) [ 61 ], Saccharomyces cerevisiae ( S. cerevisiae ) [ 61 ], Zygosaccharomyces rouxii ( Z. rouxii ) [ 61 ], Aspergillus flavus ( A. flavus ), Microspora griseus ( M. griseus ), and Trichophyton rubrum ( T. rubrum ) [ 64 ]. Notably, in some cases, their antifungal activity is comparable to reference drugs, such as Amphotericin B [ 58 ], Fluconazole [ 62 , 64 ], Voriconazole [ 64 ], and Ketoconazole [ 64 ].…”

Solid state structure of new 5-[2-(N,N-diethylamino)ethoxy]-4,7-dimethylcoumarins by X-ray and 13C CP/MAS NMR

“…We have decided to use the microwave-assisted organic synthesis, since it offers various advantages, such as selective heating, accelerated reaction rates and improved product yields [7]. We previously used microwave heating for the synthesis of a series of benzo [b]furans and coumarins, which are structurally similar to coumarins, and have obtained both increased reaction rates and yields [8,9]. To determine the structural details we applied X-ray diffraction technique.…”