Antimicrobial Compound 1

Antimicrobial Compound 1 is an alkyl pyridinium compound with Tail 12C, Head 4-carboxyl. Antimicrobial Compound 1 exhibits antimicrobial activities against B. subtilis and E. coli.

Chlamydia pneumoniae-IN-1 (compound 55), a benzimidazole derivative, exhibits potent antibacterial activity, inhibiting 99% of C. pneumoniae growth at a concentration of 10 μM while maintaining 95% viability of host cells. It effectively inhibits the CV-6 strain of C. pneumoniae with a minimum inhibitory concentration (MIC) of 12.6 μM, demonstrating its antichlamydial efficacy [1].

1. Linalool (Linalol), a natural compound of the essential oils, has been shown to have antinociceptive, antimicrobial, and anti-inflammatory properties. 2. Linalool was protected against LPS GalN-induced liver injury through induction of antioxidant defense via Nrf2 activating and reduction inflammatory response via NF-κB inhibition. 3. Linalool biosynthesis and accumulation might be involved in plant defense against bacterial and fungal pathogens and be associated with field resistance to citrus canker. 4. Linalool significantly increased the expression of antioxidant enzymes regulated by Nrf-2 and diminished lung tissue levels of several pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL)-6.

Antimicrobial agent-34 (compound 4h), characterized by its clogP value of 9.14, effectively disrupts the integrity of bacterial cell membranes. This compound boasts a minimum inhibitory concentration (MIC) ranging from 1–4 μg mL and shows notable plasma stability with an HC50 of 131.1 μg mL. Additionally, it exhibits excellent membrane selectivity, as evidenced by its HC50 MIC ratio of 65.6, and possesses rapid sterilization capabilities. It not only increases intracellular reactive oxygen species but also causes the leakage of protein and DNA, culminating in bacterial death. Antimicrobial agent-34 has demonstrated significant antibacterial effectiveness in vivo, particularly in a mouse sepsis model infected with Staphylococcus aureus ATCC43300.

ChlaDUB1-IN-1 (Compound 8) is an inhibitor of the Chlamydia deubiquitinase enzyme 1 (ChlaDUB1) and serves as a potential agent in antimicrobial research.

1-Amino-2,5-anhydro-1-deoxy-D-mannitol is a potent antibacterial compound effective against various Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Its application potential lies in its ability to combat common antibiotic-resistant bacterial infections effectively. 1-Amino-2,5-anhydro-1-deoxy-D-mannitol may emerge as a novel antimicrobial agent in clinical inhibition.

Metallo-β-lactamase-IN-16 (compound 18), a sulfone-containing metallo-β-lactamase inhibitor, exhibits antimicrobial activity. It effectively inhibits various metallo-β-lactamases, including NDM-1 (New Delhi metallo-β-lactamase-1), IMP-1 (imipenemase-1), VIM-1 (Verona Integron-encoded Metallo-β-lactamase), and VIM-2. The IC50 values for these enzymes are 0.16 nM, 0.23 nM, 0.31 nM, and 1.0 nM respectively.

Antibacterialagent 119 (Compound 21 g) is a potential antibacterial agent effective against methicillin-resistant Staphylococcus aureus, with a minimum inhibitory concentration (MIC) of less than 1 μg mL against tested strains. It induces reactive oxygen species (ROS) generation and disrupts bacterial cell membranes, causing their rupture. Antibacterialagent 119 exhibits strong antimicrobial activity, low cytotoxicity, rapid bactericidal action, and favorable in vivo antibacterial efficacy.

Antibacterialagent 258 (Compound 11e) is an antimicrobial agent capable of disrupting bacterial cell membranes and inhibiting various Gram-positive bacteria, with a MIC of 1-2 μg mL against Staphylococcus aureus. It exhibits low hemolytic activity and cytotoxicity, and demonstrates anti-infective properties in mouse models.

Biotin protein ligase-IN-1 (Compound Bio-9) is an inhibitor of biotin protein ligase (BPL) with a Kd of 7 nM. This compound exhibits antimicrobial activity, with minimum inhibitory concentration (MIC) values of 0.2 μM against Staphylococcus aureus (including MRSA and MSSA) and 20 μM against Mycobacterium tuberculosis.

Antimicrobial-IN-1 (compound 17) demonstrates potent antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), exhibiting inhibition zone diameters of 18 mm mg and 16 mm mg, respectively.

IKD-8344 is a macrocyclic dilactone originally isolated from an actinomycete species with diverse biological activities, including anticancer, antimicrobial, and anthelmintic properties [1,2,3]. It is cytotoxic to L5178Y murine leukemia cells (IC50 = 0.54 ng ml) [1], inhibits growth of the mycelial form of C. albicans (MIC = 6.25 μg ml), and potentiates the activity of polymyxin B against the multidrug-resistant pathogenic bacterium B. cenocepacia [2,3]. Additionally, it is active against T. spiralis in vitro and in vivo [1].

Diallyl tetrasulfide is an organosulfur compound that has been found in A. sativum and has diverse biological activities, including antimicrobial, antioxidant, and anticancer properties.[1],[2],[3],[4] It is active against the bacteria S. aureus and methicillin-resistant S. aureus (MRSA; MICs = 0.5 and 2 mg/L, respectively), as well as the fungi C. albicans, C. krusei, C. glabrata, A. niger, A. flavus, and A. fumigatus (MICs = 0.5, 4, 2, 1, 2, and 4 mg/L, respectively).[1] It reduces cadmium-induced increases in hepatic levels of thiobarbituric acid reactive substances (TBARS) and increases cadmium-induced decreases in the hepatic activity of superoxide dismutase (SOD1), catalase, GST, and glucose-6-phosphate dehydrogenase (G6PDH) in rats when administered at a dose of 40 mg/kg.[2] Diallyl tetrasulfide is cytotoxic to MCF-7 breast cancer cells (IC50 = 92 μM) and reduces tumor growth in a BGC-823 mouse xenograft model when administered at doses of 20, 30, and 40 mg/kg for 32 days.[3],[4]

Kigamicins are natural antitumor antibiotics that selectively kill pancreatic cancer PANC-1 cells only under nutrient-starved conditions. They also show antimicrobial activity against Gram-positive bacteria, including methicillin-resistant S. aureus. Kigamicin C inhibits PANC-1 cell survival in nutrient-deprived media at a 100-fold lower concentration than that required for cells maintained in nutrient-rich media. A related compound, kigamicin D, is active in vivo, suppressing the tumor growth of several pancreatic cancer cell lines in nude mice. It blocks the activation of Akt induced in PANC-1 cells placed in nutrient-deprived media. Kigamicin can also induce necrosis in human myeloma cells, but not normal lymphocytes, maintained in nutrient-rich media (CC50 = 100 nM).

Lactoferricin B (4-14), bovine (TFA), is a peptide derived from residues 4-14 of bovine lactoferrin, exhibiting broad-spectrum antimicrobial activity against various microorganisms[1].

Brilacidin tetrahydrochloride (PMX 30063 tetrahydrochloride) is a defensin mimetic antibiotic exhibiting potent antimicrobial activity against various bacteria, with MIC90 values of 1 μg mL for Streptococcus pneumoniae, 8 μg mL for Streptococcus viridans and Haemophilus influenzae, and 4 μg mL for Pseudomonas aeruginosa.

IDR-1 is an antimicrobial peptide active against both Gram-positive and Gram-negative bacteria. This compound modulates innate immunity to counter infections while avoiding evident toxicities. Additionally, IDR-1 exhibits anti-inflammatory and anti-infective properties, increases the levels of monocyte chemokines, and reduces the release of pro-inflammatory cytokines.

Antimicrobial agent-3 (Compound U10) is an antimicrobial agent effective against bacterial, fungal, and tubercular infections [1].

FabH-IN-1 (compound 3f) is an effective inhibitor of bacterial 3-oxoacyl-[acyl-carrier-protein] synthase 3 (FabH), a broad-spectrum antimicrobial target, demonstrating efficacy against both gram-positive and gram-negative bacteria, and exhibiting strong antioxidant properties [1].

Antimicrobial agent-2 (compound V-a) is a broad-spectrum antimicrobial agent effective against various Gram-positive and Gram-negative bacteria, with low toxicity, no obvious resistance, and good bioavailability. It damages the membrane, leading to protein leakage and inducing ROS production. It notably inhibits Methicillin-resistant Staphylococcus aureus (MRSA) with a MIC of 1 μg mL [1].

NusB-IN-1 (Compound 22r) is a highly effective, orally administered bacterial rRNA synthesis inhibitor with potent antimicrobial activity against MRSA and VRSA [1].

Metallo-β-lactamase-IN-5 (compound 5c) is a potent inhibitor of metallo-β-lactamases (MBLs), demonstrating inhibitory activity against MBLs NDM-1 and VIM-1. It effectively inhibits HUVECs with an IC50 value of 45 μg mL. Additionally, when combined with Imipenem, Metallo-β-lactamase-IN-5 exhibits synergistic antimicrobial activity [1].

Chitin synthase inhibitor 2 (compound 2b) is a highly potent inhibitor of chitin synthase, with an IC50 of 0.09 mM and a K i of 0.12 mM. This compound exhibits antimicrobial activity in vitro and demonstrates synergistic or additive effects when combined with fluconazole or polyoxin B [1].

Antimicrobial Agent-1 (compound 6C) shows strong activity (MIC = 2 μg mL) against TolC mutant E. coli. Additionally, it synergistically interacts with Colistin to exhibit enhanced activity against Gram-negative bacteria. Importantly, Antimicrobial Agent-1 exhibits no cytotoxic effects on mammalian cell lines. Its MIC values on Caco-2 and Vero cell lines are greater than 128 μg mL [1].