Monocarbonyl curcumin-quinoline molecular hybrids: Synthesis, antibacterial, and antioxidant evaluation combined with in silico predictions

Searching for different pharmacological attributes of curcumin analogous a series of 14 quinoline-based monocarbonyl curcumin derivatives were synthesized via Claisen-Schmidt condensation, achieving yields in the range of 49–88 % and evaluated for in-vitro antibacterial, antioxidant, and in-silico molecular docking studies. The prepared derivatives evaluated against Gram-negative ( Escherichia coli , Pseudomonas aeruginosa ) and Gram-positive ( Staphylococcus aureus , Staphylococcus pyogenes ) human pathogenic strains exhibited moderate to good activities compared to ciprofloxacin. Among all hybrids, 14e showed the highest inhibition zone (IZ) against Pseudomonas aeruginosa (18.00 ± 0.57 mm), and 14d exhibited broad-spectrum activities against tested bacterial strains, with IZ ranging from 17.00 ± 0 to 17.00 ± 0.057 mm. Compound 14 m exhibited notable activity against Streptococcus pyogenes , producing an IZ of 17.00 ± 0.00 mm. The DPPH radical scavenging results indicate that 14a and 14d showed the strongest radical scavenging potential with 90.50 ± 0.04 % (IC 50 3.83 μg/mL) and 91.30 ± 0.04 % (IC 50 3.31 μg/mL), respectively. The obtained values were comparable with ascorbic acid (96.00 ± 0.09 %, IC 50 2.27 μg/mL). In-silico molecular docking analysis showed all derivatives displayed strong binding affinities with protein targets (6F86: −7.0 to −8.2 kcal/mol; 3TO7: −8.0 to −9.3 kcal/mol; 5OE3: −5.0 to −9.9 kcal/mol; 6KUD: −7.5 to −8.0 kcal/mol) versus ciprofloxacin (−7.1 to −8.2 kcal/mol). Against 1DNU, derivatives scored −9.5 to −10.3 kcal/mol compared to ascorbic acid (−6.1 kcal/mol). Many compounds targeting topoisomerase IIα achieved docking scores (−8.6 to −9.8 kcal/mol), while etoposide (−8.6 kcal/mol. Overall, the synthesized compounds displayed in vitro antibacterial and antioxidant activities consistent with in-silico predictions. SwissADME analysis showed that synthesized compounds met Lipinski's Rule of Five, while ProTox-II results indicated no risk of hepatotoxicity, carcinogenicity, or cytotoxicity.