Microbiologie/Virologie

<p>SID 26681509 is a selective inhibitor of cathepsin L (IC50: 56 nM) and blocks Plasmodium falciparum (IC50: 15.4 μM) and Leishmania major (IC50: 12.5 μM).</p>

<p>Trans-Clopenthixol ((E)-Clopenthixol) is an antibiotic without any sedative properties. It can be used in vitro to inhibit Pseudomonas aeruginosa and Plasmodium falciparum.</p>

<p>Saphenamycin is an antibiotic from a strain of Streptomyces.</p>

<p>RSV-IN-5: Dual inhibitor for RSV fusion proteins, effective on wild-type A2 and D486N mutant with EC50s of 2.0 nM &amp; 8.1 nM. Potent anti-RSV.</p>

<p>LolCDE-IN-2 is a potent Lol protein (LolCDE) inhibitor. LolCDE-IN-2 shows antibacterial activity with a MIC of 2 μg/ml against E. coli MG1655 [1].</p>

<p>HIV-1 protease-IN-6 (17d) strongly inhibits HIV-1 protease (IC50: 21 pM, Ki: 4.7 pM) and effectively targets DRV-resistant mutants.</p>

<p>Anti-MRSA agent 27 (compound 4a) is a potent antimicrobial agent against methicillin-resistant Staphylococcus aureus (MRSA) with a minimum inhibitory concentration (MIC) of 0.0975 μmol/L. It effectively disrupts MRSA biofilms and inhibits the production of hemolysins.</p>

<p>A25822B is an antifungal agent.</p>

<p>β-Glucuronidase-IN-2 is a potent inhibitor of E.</p>

<p>Anti-infective agent 10 (Compound Example 30) is an ns5b polymerase inhibitor that functions as an anti-HCV agent.</p>

<p>Compound 6q, a trifluoromethylpyridine oxadiazole, targets Xanthomonas oryzae with EC50 of 7.2 μg/mL.</p>

<p>(Rac)-Plevitrexed is a racemate of Plevitrexed. Plevitrexed is an orally active and potent inhibitor of thymidylate synthase (TS).</p>

<p>Valopicitabine is an effective prodrug of the effective anti-HCV drug 2'-C-methylcytidine and can be used as a promising antiviral drug for the study of chronic</p>

<p>BDM91288, an orally active AcrB efflux pump inhibitor of pyridinium piperazine, enhances the in vivo efficacy of levofloxacin in treating Klebsiella pneumoniae pulmonary infection in mouse models [1].</p>

<p>Antibacterial agent 204 (Compd P2-56-3) enhances the activity of Rifampin (RIF) against Acinetobacter baumannii and Klebsiella pneumoniae by disrupting the outer membrane of A. baumannii. T [1].</p>

<p>EFP-IN-1: potent β-lysine derivative, inhibits EFP, slows E. coli growth.</p>

<p>Compound (S,R)-48 inhibits Pf, Pv, &amp; Tbr PRT with Ki of 50, 20, 2 nM.</p>

<p>PqsR-IN-2, potent PqsR inhibitor, curbs Pseudomonas aeruginosa communication, reduces pyocyanin, with low toxicity.</p>

<p>PFK-IN-1 (compound 1) is an inhibitor of 6-phosphofructo-1-kinase (PFK), demonstrating IC50 values of 0.41 and 0.23 μM against T. brucei and T. cruzi PFK, respectively, and an ED50 of 15.18 μg/mL for T. brucei. The compound has a half-life of 9.7 minutes in rat liver microsomes and 408 minutes in mouse liver microsomes.</p>

<p>Antibacterialagent 279 (compound A12) is an effective antibacterial agent. It inhibits the SOS response of Pseudomonas aeruginosa.</p>

<p>LN-439A (compound LN-439A) is a novel BAP1 inhibitor that suppresses the growth of basal-like breast cancer by degrading KLF5.</p>

<p>Ibafloxacine (R835) is a fluoroquinolone antibiotic that is used exclusively in veterinary applications and shows zero good bacteriostatic effect against</p>

<p>Saussureamine C is an inhibitor of H274Y and N294S mutants.</p>

<p>HIV-1 inhibitor-13: oral NNRTI, IC50=0.14μM for HIV-1 RT, effective on resistant strains (EC50=2.85-18nM).</p>

<p>BRL-42715 is an effective inhibitor of bacterial beta-lactamases.</p>

<p>Ambelline has antitumor activity.</p>

<p>ZIKV-IN-4 is a low cytotoxic, acid-stable anti-ZIKV agent with an EC50 value of 3.49 μM. ZIKV-IN-4 exhibited potent inhibition of ZIKV NS5 MTase.</p>

<p>DHX9-IN-19 (compound 3) is an orally active inhibitor of DHX9, playing a significant role in cancer research.</p>

<p>MAY0132 is a potent and selective EPAC2 inhibitor with an IC50 of 0.4 μM. It significantly inhibits the replication of HMPV, AdV, and RSV, reduces cytokine/chemokine production induced by viral infections, and suppresses NF-κB activation. MAY0132 exhibits antiviral activity and can be used in respiratory virus infection research.</p>

<p>Compound 25b inhibits DENV2/ZIKV NS2B/NS3 proteases; IC50: ZIKV 0.67μM, DENV2 4.38μM.</p>

<p>JPL is an InhA-cofactor-ligand 3FNG inhibitor and is used for the study of tuberculosis [1].</p>

<p>2'-Amino-2'-deoxyadenosine (9-(2-Amino-2-deoxypentofuranosyl)-9H-purin-6-amine) is a nucleoside antibiotic that effectively inhibits various Mycoplasma strains.</p>

<p>Arterolane, an adenosine triphosphatase inhibitor, is used potentially for the treatment of malaria.</p>

<p>InhA-IN-7 (Compound 11), a derivative of Triclocan, shows inhibitory activity against enoyl-acyl carrier protein reductase (InhA) with an IC50 of 96 nM. It effectively inhibits the proliferation of both wildtype and mutant strains of Mycobacterium tuberculosis, exhibiting minimum inhibitory concentrations (MICs) ranging from 19 to 75 μM [1].</p>

<p>Inactive enantiomer of Sofosbuvir, used for chronic hepatitis C; lacks reported biological activity.</p>

<p>BPR3P0128, a non-nucleoside RNA-dependent RNA polymerase (RdRp) inhibitor, is effective orally and can inhibit various SARS-CoV-2 variants. It exhibits EC 50 values of 0.62 µM for SARS-CoV-2 and 0.14 µM for HCoV-229E, demonstrating potent anti-pancoronavirus activity at submicromolar concentrations. Additionally, BPR3P0128 displays synergistic antiviral effects when used in combination with Remdesivir [1].</p>

<p>Polθ-IN-8 (example 77) is a DNA polymerase θ (Polθ) inhibitor with an IC50 for Polθ ATPase activity of less than 100 nM. Polθ-IN-8 is useful for researching diseases related to Polθ activity, such as cancer.</p>

<p>Metallo-β-lactamase-IN-14 (Compound 17e) serves as an inhibitor of Metallo-β-Lactamase, displaying inhibitory activity against VIM-1 and VIM-2. This compound also exhibits antibacterial effects on Gram-negative (GN) bacteria and P. aeruginosa [1].</p>

Isopyrazam, a plant protection product, exhibits potent antifungal activity. When applied to crops, it effectively inhibits the growth of various plant pathogenic fungi, significantly enhancing both the yield and quality of the crops. This compound demonstrates exceptional disease resistance capabilities in agricultural applications.

<p>Antimalarial 9, a quinoline-imidazole derivative, effectively targets CQ-susceptible (IC50-0.14 μM) and MDR strains (IC50-0.41 μM) with low toxicity.</p>

<p>MsbA-IN-2 is a potent inhibitor of the lipopolysaccharide transporter MsbA and is able to act on E. coli MsbA (IC50: 2 nM).</p>

<p>SARS-CoV-2-IN-23 (compound GRL-0617) is an inhibitor of SARS-COV-2 papain-like protease (PLpro) (IC 50 = 2.3 μM) [1].</p>

<p>ABT-072 is a nonnucleoside NS5B polymerase inhibitor and a candidate drug evaluated for treatment of hepatitis C virus.</p>

<p>CTSL/CAPN1-IN-2 (Compound 14b) serves as an orally active inhibitor targeting both CTSL and CAPN1, manifesting IC50 values of 6.88 nM for CTSL and 347.6 nM for CAPN1 respectively. This compound not only displays anti-inflammatory attributes but also features favorable pharmacokinetic properties. Moreover, CTSL/CAPN1-IN-2 shows extensive antiviral effects against coronaviruses by inhibiting viral entry [1].</p>

<p>SAG-524 is a powerful oral small molecule that inhibits HBV viral replication. In HepG2.2.15 cells, SAG-524 reduced HBV-DNA and HbsAg levels in the supernatant with IC₅₀ values of 0.92 nM and 1.4 nM, respectively [1].</p>

<p>iPAF1C is a powerful inhibitor of the polymerase-associated factor 1 complex (PAF1C) and exhibits anti-HIV activity [1].</p>

<p>Lentiginosine is a selective amyloglucosidase inhibitor.</p>

<p>Neuraminidase-IN-4 inhibits neuraminidase (EC50: 1.59 μM) and has strong anti-H5N1 activity.</p>

<p>Benzisothiazolone is an isothiazolinone fungicide that demonstrates growth inhibitory activity against Escherichia coli ATCC 8739 and yeast NCYC 1354. It is utilized in studies investigating growth inhibition models.</p>

<p>1,5-Dideoxy-1,5-imino-D-mannitol is an antibiotic with antibacterial properties.</p>

<p>Meclocycline: a tetracycline antibiotic, inhibits LDH, reduces cell toxicity from mutant huntingtin, doesn't change protein levels in PC12 cells.</p>

<p>LpxA-IN-1, a novel UDP-N-acetylglucosamine acyltransferase (LpxA) inhibitor exhibiting potent activity (IC 50 2 nM), effectively targets Pseudomonas aeruginosa</p>

<p>GR 122222X is an inhibitor of topoisomerase II.</p>

<p>Apalcillin (PC-904) combined with Ro 48-1220 (a penicillin sulfone β-lactamase inhibitor) exhibits broad-spectrum activity against Gram-negative aerobic and anaerobic bacteria, excluding Klebsiella acid-producing strains. This combination shows strong efficacy against β-lactamase-producing Moraxella catarrhalis, Haemophilus influenzae, and Neisseria gonorrhoeae with an effective MIC of 11 μg/mL. Additionally, it inhibits Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter at low MICs (0.25 to 4 μg/mL). However, it has limited efficacy against oxacillin-resistant staphylococci and some Gram-positive bacteria. Apalcillin/Ro 48-1220's effectiveness against certain extended-spectrum β-lactamase-producing Escherichia coli is comparable to piperacillin/tazobactam, though it is less effective against SHV-type β-lactamases.</p>

<p>Tenellin is a fungal metabolite that inhibits Mg2+-, Ca2+-, and Na+/K+-ATPase activities in erythrocytes. Tenellin is cytotoxic to Sf9 and Sf21 insect cells.</p>

<p>Plevitrexed, an oral TS inhibitor (Ki: 0.44 nM), targets α-folate receptor &amp; reduced folate carrier, treats gastric cancer.</p>

<p>Penethamate hydriodide is a diethylaminoethyl ester prodrug of penicillin, utilized via intramuscular injection to treat mastitis in cattle.</p>

<p>TKB272 is an orally active antiviral agent that selectively targets the main protease (Mpro) of SARS-CoV-2, effectively inhibiting the infection and replication of various strains, including Omicron variants (such as XBB.1.5 and EG.5.1). It exhibits an enzyme inhibitory activity with an IC50 of 0.7 µM against SARS-CoV-2WK-521 Mpro and shows potent antiviral activity at the cellular level with an EC50 as low as 2.6 nM in HeLahACE2-TMPRSS2 cells against the BQ.1.1 strain. TKB272 also has a CC50 of 98 µM, indicating low cytotoxicity. Furthermore, it demonstrates a significant suppression of SARS-CoV-2XBB.1.5 replication in the B6.Cg-Tg(K18-hACE2)2-Prlmn/J transgenic mouse model, suggesting potential use in the research of SARS-CoV-2 infections.</p>

<p>CMX990, a SARS-CoV-2 3CL protease inhibitor, exhibits EC90 values of 9.6 nM in human bronchial epithelial cells (HBECs) and 101 nM in HeLa-ACE2 cells. It also demonstrates good ADME and pharmacokinetic properties [1].</p>

<p>DXR-IN-3 is an anti-Toxoplasma DXR inhibitor. It exhibits in vitro activity against the TgDXR enzyme, with an IC50 value of 0.62 μM and a Ki value of 0.19 μM. Furthermore, DXR-IN-3 can inhibit the proliferation of Toxoplasma, displaying an IC50 value of 5.46 μM.</p>

<p>Massarilactone H, a polyketide, is a neuraminidase inhibitor, with an IC 50 of 8.18 µM .</p>

<p>RAD51-IN-8 inhibits RAD51-BRCA2 interaction and H4A4 with EC50 of 19 μM; a micromolar PPI inhibitor.</p>

<p>Compound 174 (Compound 5g), an antibacterial agent, exhibits potent anti-infective properties in vivo along with appreciable pharmacokinetic profiles. This highly active substance demonstrates favorable biofilm removal capabilities, low hemolysis, and acceptable mammalian cell toxicity [1].</p>

<p>Antibacterial Agent 172 (Compound 6a), a &lt;i&gt;Clostridioides difficile (Cd) SpoVD inhibitor with an IC50 value of 89 nM, effectively inhibits the sporulation of Clostridioides difficile. It is useful for research on bacterial infections [1].</p>

<p>FNC-TP trisodium, active intracellular FNC form, inhibits NRTI, fights HIV, HBV, and HCV.</p>

<p>Succinate dehydrogenase-IN-8 (compound i19) is a potent inhibitor of succinate dehydrogenase (SDH). This indanoyl amino acid derivative demonstrates strong antifungal activity in vitro against Rhizoctonia solani (EC50 = 0.1843 mg/L), Botrytis cinerea (EC50 = 0.4829 mg/L), and Sclerotinia sclerotiorum (EC50 = 0.1349 mg/L).</p>

<p>Antifungal agent 16 has antimicrobial activity comparable to that of ciprofloxacin and has higher antifungal activity than fluconazole.</p>

<p>Compound 3d: antitubercular, MIC 0.007 μg/mL vs MTB H37Rv, 1.851 μg/mL vs MDR-MTB 16833, metabolically unstable.</p>

<p>Compound 18a: potent vs. T. brucei (IC50: 0.47 μM), &gt;2x efficacy compared to Nifurtimox, good ADME, binds AT-rich DNA.</p>

<p>Alphavirus-IN-1 blocks VEEV (EC50: 0.24 μM) &amp; EEEV (EC50: 0.16 μM), non-toxic, stable in mice plasma.</p>

<p>Cefempidone (GR 50692) is a third-generation cephalosporin antibiotic. It exhibits antibacterial activity by inhibiting penicillin-binding proteins involved in the synthesis of bacterial cell walls.</p>

<p>7-APRA is a semisynthetic intermediate of the cephalosporin class of antibiotics. It exhibits antibacterial activity and is primarily used in the synthesis of other cephalosporin antibiotics, such as Cefaclor and Cefprozil.</p>

<p>Griseofulvic Acid ((±)-Griseofulvic acid) is a metabolite of the antifungal agent Griseofulvin. It induces protein aggregation and tubulin polymerization in cell-free assays.</p>

<p>Ro 24-4383 is a carbamate-linked dual-action antibacterial agent.</p>

<p>HIV-1 Inhibitor-61 (2c) serves as a potent inhibitor of HIV-1 reverse transcriptase, exhibiting an EC50 value of 0.07 nM in NL4-3 wt MT-4 cells [1].</p>

<p>Antifungal agent 38, a heterocyclic disulfide, shrinks hyphae and damages cell membranes, causing leakage.</p>

<p>Deleobuvir(BI207127) is an inhibitor of non-nucleoside hepatitis C virus NS5B polymerase for the treatment of hepatitis C.</p>

<p>LasR-IN-1 (9g) strongly inhibits LasR, potent vs E. coli, with a 28.13 μM MIC against P. aeruginosa.</p>

<p>PLpro-IN-5 (compound 21), serving as a PLPro protease inhibitor, boasts an IC50 of 91.14 nM. This compound exhibits a broad-spectrum antivirus efficacy, particularly effective against SARS-CoV, MERS-CoV, and SARS-CoV-2.</p>

<p>Bleomycin Free Base, a glycopeptide antibiotic, halts DNA function and treats solid tumors.</p>

<p>Carbodine is an antiviral targeting CTP synthetase, effective against influenza A0/PR-8/34 and A2/Aichi/2/68.</p>

Lapyrium chloride (Emcol E 607) is a broad-spectrum antibacterial agent that serves as a preservative and disinfectant.

<p>Desthiazolylmethyl ritonavir is an alkaline-catalyzed degradation product of the HIV protease inhibitor Ritonavir.</p>

<p>MA220607 is an antibacterial agent characterized by low hemolytic toxicity and a dual-target mechanism of action (MOA). It promotes FtsZ protein polymerization, increases bacterial membrane permeability, and inhibits biofilm formation. The resistance rate of MA220607 is low, with MICs against Gram-positive bacteria and Gram-negative bacteria ranging from 0.062-2 μg/mL and 0.5-4 μg/mL, respectively [1].</p>

<p>Anti-MRSA agent 3 targets MRSA with 0.098 μg/ml MIC, low toxicity, binds DNA, and disrupts cell walls/membranes.</p>

<p>MT0703 is a cephalosporin antibiotic featuring an aminothiazolylglycyl moiety with a 1,5-dihydroxy-4-pyridinone-2-carbonyl group, displaying potent activity against Pseudomonas species.</p>

<p>CM-728 is an oxazanonaphthoquinone that exhibits cytotoxic and antibacterial properties. It acts as a human peroxidase-1 inhibitor and serves as a source of oxidative stress affecting mitochondrial function.</p>

<p>Compound 15c selectively inhibits SARS-CoV-2 nsp3 Mac1 with IC50 of 6.1 μM.</p>

<p>SARS-CoV-2-IN-22 is a SARS-CoV-2 pseudovirus inhibitor (IC50: 16.96 μM).</p>

<p>L-threo-β-Hydroxyaspartic acid is an amino acid antibiotic with activity against Bacillus subtilis, Xanthomonas oryzae, Mycobacterium phlei, and Botrytis cinerea.</p>

<p>QPX7728 is an of ultra-broad-spectrum boronic acid beta-lactamase.</p>

<p>CEN inhibitor IN-17 targets influenza A/H3N2; IC50: 1.29 μM. From patent CN112898346A, DSC701.</p>

<p>Antifungal agent 19 shows the potent antifungal activity ( EC 50 = 0.72 μM).</p>

<p>TBAJ-5307 is a broad-spectrum anti-non-tuberculous mycobacteria inhibitor that targets the FO-domain of the engine, preventing rotation and proton-translocation. TBAJ-5307 inhibits non-tuberculous mycobacteria in vitro and in vivo [1].</p>

<p>HBV/HDV-IN-3 (Compd 1) acts as a dual inhibitor for HBV and HDV, demonstrating an efficacy (EC 50) below 50 nM against HBV .</p>

<p>Neocryptolepine-Cl (compound Z24) is an inhibitor of Bcthi4, demonstrating excellent antifungal activity against B. cinerea, with an EC50 value of 0.56 μg/mL.</p>

<p>HCV-IN-7: potent oral HCV NS5A inhibitor, pan-genotypic, IC50s 3-47 pM, good pharmacokinetics, favorable liver uptake.</p>

<p>XR8-69 is a SARS-CoV-2 PLpro inhibitor. XR8-69 has a low micromolar antiviral effect in SARS-CoV-2 infected human cells.</p>

<p>Ladirubicin, as an anthracyclines analog is the leading compound of alkylcyclines.</p>

<p>NIP-22c, a novel inhibitor of coronavirus 3CL pro, exhibits antiviral activity [1]. The compound's EC50 values are 4.6 μM for Verona, 1.1 μM for Calu3, 0.1 μM for Caco2, and 0.6 μM for HBTEC-ALI.</p>