Postpolymerization modification of polyvinylpyrrolidone and evaluation of anti-quorum-sensing, antimicrobial, and antibiofilm activities with molecular docking and absorption, distribution, metabolism, and excretion studies

Antibiotic resistance is a major health risk, and biocompatible polymers like polyvinylpyrrolidone and their derivatives are used in developing suitable antimicrobials. In this study, polyvinylpyrrolidone was reacted with potassium hydroxide and later coupled with benzoyl chloride (C₇H₅ClO) to produce polyvinylpyrrolidone 2. Polyvinylpyrrolidone 2 was reacted with 3-(dimethylamino)-1-propylamine to obtain polyvinylpyrrolidone 3. The polyvinylpyrrolidone derivatives were characterized using nuclear magnetic resonance and Fourier transform infrared spectroscopy. Polyvinylpyrrolidone 2 and polyvinylpyrrolidone 3 inhibited the production of violacein in Chromobacterium violaceum CV12472 and mutant strain C. violaceum CV026, indicating their potential anti-quorum-sensing properties. Polyvinylpyrrolidone 2 and polyvinylpyrrolidone 3 inhibited flagella-dependent swarming and swimming against Pseudomonas aeruginosa PA01 at minimal inhibitory concentration and sub-minimal inhibitory concentration concentrations in a dose-dependent manner. Polyvinylpyrrolidone 3 was more active than polyvinylpyrrolidone 2, which could be attributed to the introduction of the amide function. Minimal inhibitory concentration values were 0.3125 mg/mL for polyvinylpyrrolidone 3 against C. albicans and S. aureus, while those for polyvinylpyrrolidone 2 were 0.625 mg/mL against C. albicans and S. aureus. Minimal inhibitory concentration values were 1.25 mg/mL for both polymer derivatives against E. coli. Polyvinylpyrrolidone 2 and polyvinylpyrrolidone 3 inhibited biofilms against E. coli, S. aureus, and C. albicans. Polyvinylpyrrolidone 3 exhibited the highest concentration-dependent biofilm inhibition of 45.86 ± 0.15% at minimal inhibitory concentration, which reduced to 9.02 ± 0.25% at minimal inhibitory concentration/8 against S. aureus. Molecular docking indicated suitable interactions between polyvinylpyrrolidone 2 and polyvinylpyrrolidone 3 derivatives and binding sites of pathogen receptor proteins with negative binding energies, and drug-likeness predicted using Swiss ADME was appropriate. The results indicate that polyvinylpyrrolidone 2 and polyvinylpyrrolidone 3 can inhibit biofilm formation and mitigate the emergence and spread of resistant strains.