Chalcone-related small molecules as potent antibacterial and antifungal agents: Design, synthesis, In vitro, and computational approaches

Infectious diseases caused by bacteria and fungi are a global health concern due to resistance to traditional antimicrobial medications. A variety of chalcone-related small molecules have been designed, synthesized, and characterized small molecules using FTIR, NMR, and MS to find antimicrobial agents for treating these infections. These designed compounds ( 9, 11, 13 ) were evaluated for their potential inhibitory activity against five bacterial strains and one fungal strain using disc diffusion and MIC assays utilizing ampicillin and fluconazole as reference drugs. The MIC values ranged from 2.5 to 160 μg/mL, which can be attributed to improved membrane penetration and increased ligand-protein binding capability. Among them, molecule 9 exhibited a broad spectrum of antibacterial activity against gram-negative bacteria, with an MICs of 40 μg/mL against P. aeruginosa and 80 μg/mL against E. coli . Compound 11 showed potent activity against gram-positive bacteria and fungi, with a MICs of 40 μg/mL against S. aureus and 80 μg/mL against C. albicans . Furthermore, similar to in vitro study results, molecular docking demonstrated that compounds 9 and 11 had a better binding affinity against gram-positive and gram-negative bacteria and fungal species than reference drugs. Finally, physicochemical and drug-likeness results showed that all the compounds can pass Lipinski's rule of five, are absorbed through the GIT, and are suitable for oral administration.