antibiofilm

Alexidine dihydrochloride has antifungal and antibiofilm activity against a diverse range of fungal pathogens. Alexidine dihydrochloride is an anticancer agent that targets a mitochondrial tyrosine phosphatase, PTPMT1, in mammalian cells and causes mitochondrial apoptosis. Thus, Alexidine dihydrochloride has the potential to be developed as a pan-antifungal, antibiofilm drug.

Antibiofilm agent-12 (Compound C13), an antifungal belonging to the carbamate derivatives, exhibits significant antifungal activity against Candida auris, with an MIC90 of 237.9 μM. It inhibits the drug efflux pump activity of Candida auris and promotes ergosterol depletion, thereby hindering the formation of Candida auris biofilms and reducing its metabolic flexibility. Additionally, Antibiofilm agent-12 demonstrates antifungal efficacy in a C. elegans model following Candida auris infection.

Antibiofilm agent-14 (compound 11) functions as an antibiofilm agent. It exhibits antifungal activity against C.albicans SC5314, with a minimum inhibitory concentration (MIC) of 50 μM.

Antibiofilm agent-15 (Compound 17) is an antimicrobial agent that inhibits biofilm formation of both Gram-positive and Gram-negative bacteria.

Antibiofilm agent prodrug 1 (Compound 5c) demonstrates antibacterial properties by inhibiting biofilm formation and iron uptake. It effectively suppresses Pseudomonas aeruginosa PAO1 with a minimum inhibitory concentration (MIC) of 1.07 μM. In addition, Antibiofilm agent prodrug 1 exhibits anti-infective activity in Caenorhabditis elegans, enhancing the survival rate of the nematodes.

Antibiofilm agent-3 (compound 3b) is a tetraformamide antibacterial compound that effectively inhibits the plant bacterial pathogen Xanthomonas citri ssp. citri (Xcc) with a minimum inhibitory concentration (MIC) of 500 μg/mL. It also suppresses biofilm formation of Xcc, with an IC50 of 15.37 μg/mL.

Antibiofilm agent-4 is a LasR inhibitor, demonstrating optimal antibiofilm and anti-QS (quorum sensing) properties.

Antibiofilm agent-5 (compound 6c) is a multitarget antibacterial agent with potent antibiofilm activity. It induces metabolic dysfunction by inactivating lactate dehydrogenase, promoting the accumulation of reactive oxygen species, which subsequently reduces reduced glutathione and leads to bacterial oxidative damage. Antibiofilm agent-5 is applicable for studying recalcitrant biofilm-enhanced bacterial infections.

Antibiofilm agent-6 (Compound 26c) is a quorum sensing inhibitor with antibiofilm properties, effectively reducing the fluorescence intensity of PAO1-lasB-gfp and PAO1-pqsA-gfp in a concentration-dependent manner. It suppresses the production of pyocyanin and rhamnolipids and enhances the efficacy of ciprofloxacin in eradicating viable bacteria in a Pseudomonas aeruginosa (P. aeruginosa PAO1) infected mouse model.

Antibiofilm agent-7 (Compound 9) demonstrates significant antibiofilm activity with IC50 values of 60 µg/mL, 133.32 µg/mL, and 19.67 µg/mL against Staphylococcus aureus, Escherichia coli, and methicillin-resistant Staphylococcus aureus (MRSA), respectively. It also exhibits antimicrobial activity with MIC values of 4.88 µg/mL, 78.13 µg/mL, 9.77 µg/mL, and 39.06 µg/mL against Staphylococcus aureus, Escherichia coli, Candida albicans, and MRSA, respectively.

Antibiofilm agent-8 (compound Ru2) boosts antibacterial activity under visible light (400-700 nm, 10 J cm-2). It induces oxidative stress by promoting NADH oxidation and reactive oxygen species (ROS) generation, which disrupts the bacterial cell wall.

Antibiofilm agent-17 is a dual-action biofilm inhibitor (IC50 = 0.33 μM) targeting Pseudomonas aeruginosa. It inhibits biofilm growth by reducing virulence production regulated by the quorum sensing system and decreasing iron acquisition capability. In a mouse wound infection model, Antibiofilm agent-17 shows synergistic antibacterial activity. This compound is useful for research on combating Pseudomonas aeruginosa infections.

Antibiofilm Agent-2 (Compound 4T) serves as a potent biofilm inhibitor, exhibiting an IC50 of 3.6 μM, and impairs the quorum sensing system along with iron homeostasis, acting as antibacterial synergists against Pseudomonas aeruginosa [1].

Antibiofilm agent-9 (Compound 4), a derivative of pyrrolnitrin, exhibits antimicrobial activity. It inhibits Bacillus anthracis with a Minimum Inhibitory Concentration (MIC) of 0.031 μg/mL. The compound demonstrates significant antibiofilm activity, achieving an inhibition rate of 84% after 24 hours at a concentration of 8.0 μg/mL. Additionally, Antibiofilm agent-9 shows favorable pharmacokinetic properties in mouse models.

Antibiofilm agent-11 (compound C12) is a flavonoid derivative with antibiofilm activity.

Antibiofilm agent-13 (compound 14b) is an effective broad-spectrum antibacterial agent that functions by disrupting the integrity of bacterial cell membranes. It achieves this through the degradation of transmembrane potential and increased membrane permeability, which leads to the production of intracellular ROS and the leakage of DNA and proteins, ultimately resulting in bacterial death. Antibiofilm agent-13 effectively inhibits both Gram-positive bacteria (MIC ranging from 0.5-1 μg/mL) and Gram-negative bacteria (MIC ranging from 1-32 μg/mL).

Antibiofilm Agent-1, as detailed in WO2017011725A1 (compound 17) [1], serves as an antibacterial agent effective against Gram-positive pathogens.

Tridecanoic acid (Tridecylic Acid) is a 13-carbon saturated fatty acid found in dairy products and also as a product of anaerobic biodegradation of n-hexadecane. It has been identified as a substrate of phospholipase A2.

3,5-Di-tert-butylphenol induces accumulation of reactive oxygen species. 3,5-Di-tert-butylphenol exhibits anti-biofilm and antifungal activities.

Trans-2,3,4-Trimethoxycinnamic acid, a natural derivative of cinnamic acid, competitively inhibits the binding of 3-oxo-C8-HSL to TraR and exhibits good antitoxic activity and antibiofilm activity against Escherichia coli.

Quorum sensing-IN-8 (compound 5e) exhibits antibiofilm activity and can be used in research on antibiotic resistance.

Anti-MRSA agent 23 (compound 11) is a potent agent against methicillin-resistant Staphylococcus aureus. This compound exhibits both antibacterial and antibiofilm properties. It facilitates the healing and reconstruction of MRSA-infected skin wounds by reducing bacterial load, alleviating inflammation, and promoting angiogenesis.

DNA Gyrase-IN-15 (Compound 11) is an antibacterial agent that inhibits both DHPS and DNA gyrase, with IC50 values of 1.73 and 0.07 µM, respectively. It shows antimicrobial activity against Enterococcus faecium (MIC of 15.62 µg/mL), Acinetobacter baumannii, Enterobacter (MIC of 7.81 µg/mL), Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus. Additionally, DNA Gyrase-IN-15 exhibits antibiofilm activity against Enterococcus faecium.

MurA-IN-5 (compound 4c) demonstrates a minimum inhibitory concentration (MIC) of 1.95 μg/mL against Escherichia coli and exhibits significant potency as a MurA inhibitor with an IC50 of 3.77 μg/mL. It also shows antibiofilm activity against various microorganisms, indicating its potential in combating biofilm-related infections.