pathogenic

Olorofim（F-901318）is a novel selective antifungal compound targeting pyrimidine biosynthesis in mycobacteria, with inhibitory effect on Aspergillus fumigatus DHODH (IC50: 44 nM), but little inhibitory effect on human DHODH (>100 uM).Olorofim has good efficacy against a variety of pathogenic filamentous and dimorphic fungi, such as Penicillium spp, P. dermatitidis spp and Fusarium spp.

BC-7013 is a novel pleurophytin with antimicrobial activity that inhibits the activity of gram-positive pathogenic bacteria and can be used in the study of skin and respiratory infections.

Gastric mucin, a large glycoprotein, is thought to play a major role in protecting the gastrointestinal tract from acid, proteases, pathogenic microorganisms, and mechanical trauma.

Fenhexamid (Elevate), a sterol biosynthesis inhibitor, shows antifungal activity against the plant pathogenic fungus. Fenhexamid is used for agriculture and is present in measurable amounts in fruits and vegetables.

Benzylideneacetone, a monoterpene produced by the insect pathogenic bacterium Xenorhabdus nematophila, is a phospholipase A2 (PLA2) inhibitor with inhibitory effects on arachidonoid biosynthesis and enhances baculovirus pathogenicity of Xylaria minor.

CRK12-IN-1 is a potent CRK12 inhibitor with insecticidal activity and exhibits inhibitory effects on Trypanosoma brucei (T.b. brucei) and Trypanosoma congolense (T. congolense) with EC50s of 1.3 and 18 nM, respectively, rapidly killing the pathogenic cells.

Uridine diphosphate glucuronic acid ammonium (UDP-α-D-glucuronic acid ammonium) is a precursor of many plant cell wall polysaccharides and is required for the production of seed mucilage.Uridine diphosphate glucuronic acid ammonium is a precursor of pathogenic fungi. ammonium is a key metabolite for pod polysaccharide synthesis in the pathogenic fungus Cryptococcus neoformans.

IRBP acetate(211426-18-5 free base) (Interphotoreceptor Retinoid Binding Protein Fragment IRBP) is a 20-residue peptide, which is a major pathogenic epitope. It exists in the first homologous repeat of interstitial visual pigment Binding Protein peptide (IRBP 161-180) and can induce post-uveitis (EAU).

Inz-1 is an effective and fungal-selective inhibitor of mitochondrial cytochrome bc1 with IC50s of 8.092 and 45.320 μM for yeast and human. Inz-1 reverses Fluconazole or other triazole antifungals’ resistance in the pathogenic fungus Candida albicans.

1,3,6,8-Tetrahydroxynaphthalene (T4HN) is a crucial precursor of 1,8-dihydroxynaphthalene-melanin, an important virulence factor in pathogenic fungi, and is believed to be the direct product of pentaketide synthases.

Pyribencarb, a benzylcarbamate-type fungicide, exhibits broad-spectrum activity against various plant pathogenic fungi. Acting as a potent Qo inhibitor of cytochrome b, Pyribencarb demonstrates particular efficacy against Botrytis cinerea and Sclerotinia sclerotiorum.

MBX2329 is a specific inhibitor of HA-mediated viral entry that inhibits H1N1 virus strain high pathogenic avian influenza H5N1 virus strain.

Totarol ((+)-Totarol) shows antibacterial effects against several pathogenic Gram-positive bacteria, mycobacterium tuberculosis.

PK150 shows oral bioavailability and antibacterial activity against several pathogenic strains at submicromolar concentrations.

Monocaprylin (Sefsol 318) is a monoglyceride of caprylic acid with an excellent antibacterial activity. Monocaprylin inhibits a variety of foodborne pathogenic and spoilage microorganisms and has the potential for an alternative food preservative research.

Bisdionin C is a potent inhibitor of GH18 chitinase with an IC50 of 0.2 μM for A. fumigatus ChiB1. Bisdionin C inhibits human macrophage chitotriosidase(HCHT, IC50 = 8.3 μM) and acidic mammalian chitinase (AMCase, IC50 = 3.4 μM).

Eugenitol (Compound 3), an antifungal metabolite extracted from Diaporthe eucalyptorum, exhibits inhibitory properties against four plant pathogenic fungi: Alternaria solani, Botrytis cinerea, Fusarium solani, and Gibberella saubinettii [1].

(Gln22)-Amyloid β-Protein (1-42), a Dutch mutation (E22Q) variant of β-Amyloid (1-42), exhibits enhanced fibrillogenic and pathogenic properties [1].

Tosatoxumab (AR-301; KBSA301), a human immunoglobulin G1 monoclonal antibody, specifically targets and neutralizes S. aureus alpha-toxin (alpha-hemolysin; Hla) by binding to its N-terminal epitope. This interaction blocks the toxin's ability to form functional pore oligomers, crucial for its pathogenic activity. As a result, Tosatoxumab offers promising potential as an adjunctive passive immunotherapy alongside conventional antibiotics for S. aureus pneumonia [1] [2].

K4 peptide exhibits potent antimicrobial properties, effectively targeting both Gram-positive and Gram-negative bacteria, particularly pathogenic strains like Staphylococcus aureus and Marine Vibrio species [1].

Gliotoxin-13C13is intended for use as an internal standard for the quantification of gliotoxin by GC- or LC-MS. Gliotoxin is an immunosuppressive mycotoxin produced by pathogenic strains ofAspergillusand other fungi with diverse biological activities.1,2,3,4,5,6,7,8It inhibits 20S proteasomal chymotrypsin activity (IC50= 10 μM), blocking the degradation of IκBα and preventing the activation of NF-κB.2,3Gliotoxin induces apoptosis in monocytes and dendritic cells and reduces phagocytosis by neutrophils.4,5It suppresses viral infection by Nipah and Hendra virus in HEK293T cells (IC50s = 149 and 579 nM, respectively).6Under reducing conditions, gliotoxin inhibits leukotriene A4hydrolase epoxide hydrolase activity, but not aminopeptidase activity, and leukotriene B4synthesis in neutrophils and monocytes.7

Funiculosin, a neutral lipophilic antibiotic, demonstrates inhibitory effects against both DNA and RNA viruses, in addition to possessing antifungal properties. It effectively combats infections induced by pathogenic fungi within primary chicken embryo fibroblasts [1].

Antifungal agent 73 (compound A32) effectively combats azole-resistant candidiasis by disrupting the fungal cell wall and membrane, demonstrating potent in vivo activity against pathogenic fungi, including fluconazole-resistant strains [1].

Terpenomycin is a polyene compound isolated from pathogenic Nocardia terpenica strains in humans, exhibiting both cytotoxic and antifungal activities [1].

7,10-dihydroxy-8(E)-Octadecenoic acid is a hydroxy fatty acid and metabolite of oleic acid that is produced byP. aeruginosafrom vegetable oils.1It is active against the food-borne pathogenic bacteriaS. aureus,S. typhimurium,L. monocytogenes,B. subtilis, andE. coli(MIC50s = 31.3, 125, 125, 62.5, and 250 μg/ml, respectively), as well as the plant pathogenic bacteriaErwinia,R. solanacearum,C. glutamicum, andP. syringae(MIC90s = 125, 125, 250, and 500 μg/ml, respectively).2,1 1.Sohn, H.-R., Bae, J.-H., Hou, C.T., et al.Antibacterial activity of a 7,10-dihydroxy-8(E)-octadecenoic acid against plant pathogenic bacteriaEnzyme Microb. Technol.53(3)152-153(2013) 2.Chen, K.Y., Kim, I.H., Hou, C.T., et al.Monoacylglycerol of 7,10-dihydroxy-8(E)-octadecenoic acid enhances antibacterial activities against food-borne bacteriaJ. Agric. Food Chem.67(29)8191-8196(2019)

Benanomicin A is a microbial metabolite found in Actinomycetes with antifungal, fungicidal, and antiviral activities. It is effective against various mammalian and plant pathogenic fungi, including C. albicans, T. mentagrophytes, C. neoformans, P. oryzae, and A. niger (MICs = 3.13-50 μg ml). Benanomicin A also inhibits HIV-1 viral infection in MT-4 cells in a concentration-dependent manner.

Pradimicin A derivative 26 exhibits antifungal, antiviral, and antiparasitic properties by attaching to d-mannose (Man)-rich glycans in pathogenic organisms [1].

Coronatine, synthesized by Pseudomonas syringae, mimics bioactive jasmonic acid conjugates or octadecanoid signal molecules in higher plants, inducing pathogenic symptoms. It enhances the virulence of Pseudomonas syringae by triggering a signaling cascade that suppresses salicylic acid accumulation, thereby promoting infection [1] [2] [3] [4].

NLRP3 antagonist 1 shows potential for the cancer research that is a potent NLRP3 antagonist. NLRP3 is involved in the body's intrinsic immunity against stress injury and pathogenic infections that is mainly expressed in macrophages and neutrophils [1].

Carbazomycin B is a bacterial metabolite found in Streptomyces with diverse biological activities. It exhibits activity against seven fungi, seven bacteria, P. falciparum, C. albicans, and five plant pathogenic fungi. Carbazomycin B is cytotoxic to MCF-7, KB, NCI H187, and Vero cells, and inhibits 5-lipoxygenase (5-LO) activity in RBL-1 cell extracts (IC50 = 1.5 µM).

Benanomicin B is a microbial metabolite that has been found inActinomycetesand has antifungal, fungicidal, and antiviral activities.1,2It is active against a variety of mammalian and plant pathogenic fungi, includingC. albicans,T. mentagrophytes,C. neoformans, andP. oryzae(MICs = 1.56-50 μg/ml).1Benanomicin B inhibits HIV-1 viral infection in MT-4 cells in a concentration-dependent manner.2 1.Takeuchi, T., Hara, T., Naganawa, H., et al.New antifungal antibiotics, benanomicins A and B from an actinomyceteJ. Antibiot. (Tokyo)41(6)807-811(1987) 2.Kondo, S., Gomi, S., Ikeda, D., et al.Antifungal and antiviral activities of benanomicins and their analoguesJ. Antibiot. (Tokyo)44(11)1228-1236(1990)

OM173-αA is a quinone bacterial metabolite that inhibits the growth of the bacteria M. gallisepticum, M. pneumoniae, and S. aureus. OM173-αA also inhibits the growth of the plant pathogenic fungus P. oryzae and several species of Trichophyton.

Rustmicin is a 14-membered macrolide identified as an inhibitor of plant pathogenic fungi.

Antifungal agent 28 (compound 18) is a selective and potent antifungal agent that disrupts mature Candida biofilms and inhibits pathogenic strains of Candida albicans and non-Candida albicans, including fluconazole-resistant strains.

Fluconazole (hydrate) is a triazole antifungal agent used for oral treatment and prevention of both superficial and systemic fungal infections, including but not limited to balanitis, various Candida infections, Cryptococcus infections, dermatomycosis, and fungal infections of the respiratory and urinary tracts. As the hydrate salt form of fluconazole, it exhibits antifungal activity by inhibiting the growth and development of pathogenic fungi, such as Candida species, at minimal inhibitory concentrations often exceeding 100 mg l. Notably, it disrupts the branching and hyphal formation in C. albicans at concentrations as low as 0.3 mg l, indicating its potency compared to other antifungals like miconazole and ketoconazole which are effective at 100-fold lower concentrations. Clinical studies have not shown a significant increase in the risk of most birth defects with oral fluconazole, although there may be an associated risk of tetralogy of Fallot. Its efficacy against Cryptococcus gattii in koalas suggests it may be ineffective as a sole therapeutic agent at a dosage of 10 mg kg orally every 12 h. Toxicity symptoms from overdose can include hallucinations and paranoid behavior.

Pterophyllin 2 is an agent of natural antifungal. It also against postharvest fruit pathogenic fungi.

Pyrenocine A is a fungal metabolite that has been found inP. terrestrisand has diverse biological activities.1It inhibits the asexual spore germination of the plant pathogenic fungiF. oxysporum,F. solani,M. hiemalis, andR. stolonifer(EC50s = 14, 20, 20, and 25 μg/ml, respectively). Pyrenocine A is active againstB. subtilis,S. aureus, andE. coli(IC50s = 30, 45, and 200 μg/ml, respectively). It inhibits onion seedling elongation (EC50= 4 μg/ml). Pyrenocine A is also a phytotoxin that inhibits lettuce seed germination and rice seedling elongation.2,3 1.Sparace, S.A., Reeleder, R.D., and Khanizadeh, S.Antibiotic activity of the pyrenocinesCan. J. Microbiol.33(4)327-330(1987) 2.Sato, H., Konoma, K., and Sakamura, S.Phytotoxins produced by onion pink root fungus, Pyrenochaeta terrestrisAgric. BioI. Chem.43(11)2409-2411(1979) 3.Sato, H., Konoma, K., Sakamura, S., et al.X-Ray crystal structure of pyrenocine A, a phytotoxin from Pyrenochaeta terrestrisAgric. BioI. Chem.45(3)795-797(1981)

RO-57-Bpyne is a γ-secretase modulator photoaffinity probe. It also can be exploited to reduce levels of pathogenic Aβ species. It acts by identifying distinct allosteric binding sites on presenilin.

Kalafungin antimicrobial agent that is inhibitory in vitro against a variety of pathogenic fungi, yeasts, protozoa, gram-positive bacteria, and, to a lesser extent, gram-negative bacteria.

Picrasidine S shows the potent cytotoxicity against human HeLa cervical, gastric MKN-28, and mouse melanoma B-16 cancer cells, it also shows the potent antibacterial activity against two strains of pathogenic bacteria methicillin-resistant Staphylococcus

Methyllinderone is a human chymase inhibitor, it has antioxidant property, it also shows moderate to weak antifungal activities against various pathogenic fungi.

Rozanolixizumab (RYSTIGGO) is a high-affinity humanized immunoglobulin G4 monoclonal antibody targeting Fc receptors (FcRn) in human newborns for the study of pathogenic IgG in autoimmune and alloimmune diseases.

20S Proteasome activator 1 is a 20S proteasome activator with IC50 values of 0.3 μM for trypsin-like sites, 0.7 μM for chymotrypsin-like sites, and 1.8 μM for caspase sites. It prevents the accumulation of pathogenic alpha-synuclein (A53T) mutants through translation in the cellular system, thereby reducing the probability of disease occurrence. 20S Proteasome activator 1 can be used to study neurodegenerative diseases.

Corypalmine is a kind of alkaloid from Coptis chinensis and purple chinensis, which has inhibitory effect on the germination of plant pathogenic spores and saprophytic fungi.

DprE1-IN-9 (compound B18) is an efficient, reversible inhibitor of DprE1, interacting with the enzyme's receptor cavity. It exhibits potent antimycobacterial properties, demonstrating activity against non-pathogenic H37Ra (MIC=0.18 µg mL) and pathogenic strains, including H37Rv, as well as clinical MDR and XDR isolates [1].

8-Hydroxy-3,5,6,7,3',4'-hexamethoxyflavone may exhibit antifungal activity against both phytopathogenic and human pathogenic fungi.

Kanosamine hydrochloride is an antibiotic that inhibits the growth of plant-pathogenic oomycetes, certain fungi, and a few bacterial species. It shows inhibitory activity against Phytophthora medicaginis M2913 and Aphanomyces euteiches WI-98 with minimum inhibitory concentrations (MICs) of 25 and 60 μg mL, respectively.

Cerebroside C is a fungal metabolite and glycosphingolipid that has been found in the rice pathogenic fungusM. grisea.1It induces production of the phytoalexin momilactone A when applied to wounded rice leaves, indicating that cerebroside C is an elicitor of the hypersensitive response in rice. Cerebroside C increases germination rate and reduces germination time in wheat seeds in a concentration-dependent manner at 4°C.2It also increases root length, fresh weight, and dry weight of wheat seedlings when used at a concentration of 20 μg/ml at 4°C, indicating increased chilling tolerance. 1.Koga, J., Yamuchi, T., Shimura, M., et al.Cerebrosides A and C, sphingolipid elicitors of hypersensitive cell death and phytoalexin accumulation in rice plantsJ. Biol. Chem.273(48)31985-31991(1998) 2.Li, H.-X., Xiao, Y., Cao, L.-L., et al.Cerebroside C increases tolerance to chilling injury and alters lipid composition in wheat rootsPLoS One8(9)e73380(2013)