Design and synthesis of β-carboline-benzofuran based hybrids as antibacterial agents against Staphylococcus aureus

The significant threat posed by Staphylococcus aureus (MRSA) is attributed to various antibiotic resistance and its role in severe infections. As an approach to combat this, a series of novel β-carboline-benzofuran based molecular hybrids were designed, synthesized, and evaluated for their antibacterial activity against Staphylococcus aureus ATCC 29213. Among the series, the minimum inhibitory concentration (MIC) of key compounds 13e, 13 h, and 13q was determined to be 4 μg/mL, compared to ciprofloxacin 0.125 μg/mL. The docking results also supported the potent compounds' ability to inhibit DNA gyrase. These compounds demonstrated bacteriostatic effects at higher concentrations, with significant inhibition of biofilm formation (MBIC₅₀ ranging from 12.78 to 30.68 μg/mL). Additionally, the compounds displayed minimal cytotoxicity against HepG2 cells and inhibited DNA gyrase, which is proven by DNA supercoiling assays and molecular docking studies. In addition, ADMET predictions indicated favorable drug-like properties, adhering to Lipinski's rule of five. These findings suggest that the synthesized β-carboline-benzofuran hybrids possess significant potential as leads for developing new antibacterial agents against MRSA.