Synthesis and anti-methicillin-resistant Staphylococcus aureus activity of 5,7-dibromo-2-benzoylbenzofurans alone and in combination with antibiotics

• Published in: Synthetic communications Vol. 51; no. 5; pp. 786 - 796
• Main Authors: Phan, Phuong-Thuy T., Nguyen, Hong-Nhung T., Kim, Son N., Pham, Tuan-Anh N.
• Format: Journal Article
• Language: English
• Published: PHILADELPHIA Taylor & Francis 04.03.2021; Taylor & Francis Ltd
• Subjects: Antibacterial activity; antibacterial synergy; antibiotic combination; Antibiotics; benzofuran; Bromides; Carboxylic acids; Chemistry; Chemistry, Organic; Dilution; Functional groups; Gentamicin; MRSA; Physical Sciences; Rap-Stoermer condensation; Science & Technology; Staphylococcus infections; Toxicity; antibiotic combination; benzofuran; MRSA; Stoermer condensation; Antibacterial activity; antibacterial synergy; Rap&#8211
• ISSN: 0039-7911; 1532-2432
• DOI: 10.1080/00397911.2020.1855354

A series of 5,7-dibromo-2-benzoylbenzofurans were synthesized by the Rap-Stoermer condensation of 5,7-dibromosalicylaldehyde with diverse phenacyl bromides and evaluated for in-vitro antibacterial activities against methicillin-sensitive Staphylococcus aureus (MSSA) ATCC 29213, methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, and MRSA ATCC 33591 by agar dilution method. The synergistic effects were determined by using the agar dilution checkerboard assay. The derivatives bearing carboxylic acid functional groups exhibited reasonable activity against MRSA strains with the best MIC = 32 µg/mL (9b, 9d). Moreover, the additive or synergistic interactions against MRSA strains was observed in six combinations (1b + cefuroxime/gentamicin, 1c + ciprofloxacin/gentamicin, 9b + gentamicin, and 9c + ciprofloxacin) with the fractional inhibitory concentration index (FICI) values in the range of 0.375-1.0. Significantly, the MICs of these antibiotics were reduced 2-4-fold. The results of the MTT assay illustrated the low mammalian cell cytotoxicity of these potent compounds.