Microbiologie/Virologie

<p>DC-159a, an 8-methoxy fluoroquinolone, possesses broad-spectrum antibacterial activity, with a particular efficacy against Gram-positive pathogens. The MIC90 values for DC-159a are 0.5 μg/mL against Streptococcus anginosus group, 4 μg/mL against Clostridium difficile, and 2 μg/mL against Bacteroides fragilis.</p>

<p>Anticaries agent-1 (Compound 21b) is utilized as an anticaries agent. It effectively inhibits biofilm formation with an IC50 of 77 μM and restricts the growth of S. mutans.</p>

<p>Antifungalagent 125 (compound 4H) is a potent succinate dehydrogenase (SDH) inhibitor with an IC50 of 3.59 μg/mL and exhibits fungicidal activity against Alternaria alternata.</p>

<p>CDA-IN-2 (Compound VS#2-3) is an inhibitor of chitin deacetylase (CDA) that exhibits antifungal properties. At a concentration of 100 μM, it inhibits P. xanthii's CDAPxCDA1 by 83.7% and PxCDA2 by 74.5%. CDA-IN-2 is applicable in research on agricultural fungal diseases, including resistance to powdery mildew and gray mold.</p>

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

<p>Glutamate-5-kinase-IN-2 (compound 54) is a potent G5K inhibitor with 4.2 μM MIC, potential in anti-TB research.</p>

<p>SARS-CoV-2 nsp14-IN-2: Strong Nsp14 methyltransferase inhibitor (IC50: 0.09 μM), potential for COVID-19 research.</p>

<p>Antibacterial agent 78 (compound 30) is an antibacterial agent with improved cytotoxicity profile[1].</p>

<p>BAR-072 is a small molecule inhibitor targeting TraE with a KD value of 2.7 µM. It significantly suppresses the transfer of the antibiotic resistance-associated plasmid pKM101. BAR-072 holds promise as a candidate molecule for research in disease areas related to infection and resistance control, by inhibiting the spread of bacterial resistance genes.</p>

<p>Palmitanilide (Palmitic acid anilide) is an antimicrobial agent effective against Gram-positive bacteria. It can electrostatically bind to components of the cell wall of Gram-positive bacteria (such as Bacillus cereus), altering the membrane structure and affecting normal cellular functions. Palmitanilide shows potential for research into infections caused by Gram-positive bacteria.</p>

<p>Erythromycin B exhibits antimalarial activity by effectively inhibiting the asexual growth of Plasmodium falciparum.</p>

<p>Antimalarial agent 44 (Compound 3) is an antiparasitic agent effective against malaria. It exhibits good permeability in MDCK-MDR1 cell monolayers and has a high clearance rate in mouse liver microsomes.</p>

<p>MTI013 is a selective inhibitor of SARS-CoV-2 nsp14 Mtase (IC50: 2.98 µM) and an antiviral agent (IC50: 10.33 µM in HCoV-229E infected Huh7 cells). Additionally, MTI013 demonstrates synergistic antiviral effects when used in conjunction with the RdRp inhibitor SHEN26.</p>

<p>MLEB-22043 is a synthetic siderophore-monocyclic β-lactam conjugate which enters bacteria through TonB-dependent transport proteins utilizing its siderophore component, subsequently exerting antibacterial activity via its β-lactam portion. This compound acts as a broad-spectrum antibiotic, exhibiting significant inhibitory activity against pathogens such as Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa.</p>

<p>Ac-Atovaquone, an ester-acetylated derivative of atovaquone, acts as a potent inhibitor of cytochrome bc1 (cytochrome bc1). This compound shows potential for use in malaria research.</p>

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

<p>2,5-Di-tert-butyl-1,4-benzoquinone is a potent antibacterial agent found primarily in marine Streptomyces sp. VITVSK1, effective against emerging antibiotic resistance. Additionally, it serves as a powerful inhibitor of RNA polymerase.</p>

<p>SARS-CoV-2 Mpro-IN-34 (Compound 26) acts as an inhibitor of SARS-CoV-2 Mpro with an IC50 of 6 nM. It also inhibits OC43 Mpro, demonstrating an IC50 of 33 nM. Furthermore, this compound exhibits antiviral activity in Vero E6 cells infected with SARS-CoV-2, with an EC50 of 0.103 μM.</p>

<p>Cefamandole (lithium), a second-generation broad-spectrum cephalosporin antibiotic, exhibits antimicrobial activity. Upon metabolism in the body, it releases free NMTT, which can lead to hypoprothrombinemia.</p>

<p>Cilastatin ammonium salt is an antibiotic that is particularly effective against Gram-positive cocci, with a half-life of 3-4 hours.</p>

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

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

<p>Compound 34e inhibits DENV2/ZIKV proteases; IC50: 0.69 µM (DENV2), 1.04 µM (ZIKV).</p>

<p>DNDI-8219 is an antitubercular agent. It has potent antileishmanial effects.</p>

<p>HBV-IN-20 is a potent, orally active HBV inhibitor (EC50: 0.46 μM). HBV-IN-20 is a classical type II CpAM (core protein assembly regulator).</p>

<p>Ciluprevir is a selective HCV NS3 protease inhibitor, effective against non-genotype-1 HCV; less potent for genotypes 2/3.</p>

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

<p>Valopicitabine, a NS5B inhibitor, is used potentially for the treatment of HCV infection.</p>

<p>Antimicrobial Agent-29 (Compound C35) influences the interaction between human hemoglobin and the Staphylococcus aureus IsdB hemophore. This compound facilitates the identification of IsdB:Hb PPI inhibitors [1].</p>

<p>SARS-CoV-2 PLpro-IN-1 (Compound 85) is a non-covalent competitive inhibitor of SARS-CoV-2 PLpro with an IC50 value of 15.06 μM and a Ki value of 22.93 μM. It inhibits the proliferation of Vero cells, exhibiting an IC50 of 7.47 μM.</p>

<p>Antileishmanial agent-6: potent against Leishmania donovani, IC50 0.54μM; cytotoxic IC50 10.2μM.</p>

<p>Amicoumacin A has antibacterial activity. It also strongly suppresses inflammatory and ulcer activity.</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>Antiviralagent 67 (compound PC6) is an inhibitor of DENVNS5 (RNA-dependent RNA polymerase) with a Ki value of 1.12 nM.</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>Antifungal agent 100 (compound 3i) demonstrates notable antifungal activity, exhibiting an EC 50 of 0.33 mg/L against S. sclerotiorum. It also possesses an IC 50 value of 0.63 mg/mL targeting the Succinate dehydrogenase (SDH) of the same organism [1].</p>

<p>Compound 7b (Antibacterial agent 99) is an effective agent with antibacterial, antifungal properties and no haemolytic activity.</p>

<p>Anti-Trypanosoma cruzi agent-1 (Compd E5) has a potent anti-Toxoplasma effect.</p>

<p>SARS-CoV-2-IN-82 (compound A) acts as an inhibitor of the Programmed-1 ribosomal frameshift (-1 PRF) in SARS-CoV-2 [1].</p>

<p>Metallo-β-lactamase-IN-13 (Compound 13i) serves as a pan Metallo-β-Lactamase inhibitor with extended activity against Gram-negative (GN) bacteria expressing metallo-β-lactamases. It exhibits antibacterial properties effective against P. aeruginosa [1].</p>

<p>Compound 9b inhibits CHS with an IC50 of 0.21 mM; it's a broad-spectrum antifungal, effective against resistant strains.</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>L 689065 is a 5-lipoxygenase inhibitor.</p>

<p>Antibiofilm agent-4 is a LasR inhibitor, demonstrating optimal antibiofilm and anti-QS (quorum sensing) properties.</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>Antifungal 42 blocks biofilm formation and inhibits C.albicans' CYP51.</p>

<p>GC-78-HCl is an orally active, non-peptidic SARS-CoV-2 Mpro inhibitor with an enzyme IC50 of 0.19 μM. It exhibits strong anti-coronavirus activity and favorable pharmacokinetic 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>5-Fluorouridine 5'-phosphate acts as an ODCase (uridine 5'-monophosphate decarboxylase) inhibitor, exhibiting a Ki value of 98 µM for human ODCase and 645 µM for Methanococcus jannaschii ODCase. This compound also shows inhibitory activity on leukemia and lymphoma cell lines, making it useful for cancer research studies.</p>

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

<p>QPX7728 bis-acetoxy methyl ester is an inhibitor of boronic acid β-lactamase.</p>

<p>Pks13-TE inhibitor 4 (compound 44) is a potent inhibitor from the thiazole series that effectively targets Pks13 to combat tuberculosis (TB) and addresses drug resistance.</p>

<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>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>DNA polymerase-IN-6 (Compound 27) exhibits inhibitory activity against DNA polymerase, with EC50 values of 0.33 µM for HCMV, 1.9 µM for HSV-1, 0.76 µM for HSV-2, and 0.066 µM for EBV.</p>

<p>ACHN-975 TFA is a selective LpxC inhibitor with a subnanomolar inhibitory. It is against a wide range of gram-negative bacterias with low MIC values (≤1 μg/mL).</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>WRN inhibitor 13 is an inhibitor of the WRN helicase with a pIC50 value ranging from 6 to 7.</p>

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

<p>8-Hydroxyerythromycin A is a semi-synthetic antibiotic with antibacterial activity.</p>

<p>Aurantiogliocladin is a mild antibiotic effective against Staphylococcus epidermidis, but it shows no efficacy against Staphylococcus aureus. It is also capable of inhibiting biofilm formation.</p>

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

<p>GS-9822 is a new LEDGIN inhibitor targeting LEDGF/p75 to alter HIV integration, showing a block-and-lock effect in cells.</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>RAD51-IN-6, a potent RAD51 gene inhibitor, may help research mitochondrial disorders. (WO2021164746A1, cmpd 23)</p>

<p>BM635 mesylate inhibits MmpL3; kills Divergent bacterium with 0.6 µM MIC50; boosts bioavailability.</p>

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

<p>Compound 112: Powerful antibacterial, MIC 1250 μM against B. subtilis, E. coli, E. faecalis, S. typhimurium, S. aureus; also an HIV-1 antibody.</p>

<p>Lamivudine, a drug for HIV-1 and HBV, inhibits reverse transcriptase and resembles zalcitabine.</p>

<p>20S Proteasome-IN-4: brain-penetrant, parasite-specific, oral, inhibits T.b. brucei proteasome (IC50: 6.3nM), for HAT research.</p>

<p>MTH1 activator-1 is an MTH1 activator that enhances endogenous MTH1 activity and significantly reduces 8-oxo-dG levels in cellular DNA. It is useful for investigating the upregulation of oxidative damage repair in nucleotide pools and examining biological effects, as well as for studies aiming to delay or prevent tumorigenesis.</p>

<p>QPX7728 methoxy acetoxy methy ester is an inhibitor of boronic acid β-lactamase.</p>

<p>Metesind Glucuronate is an antineoplastic. It also is a specific thymidylate synthase inhibitor.</p>

<p>Compd 3b: anti-trypanosomal, IC50 0.51 μM (NINOA), 3.06 μM (INC-5), also combats T. gondii.</p>

<p>ABT-072 is a nonnucleoside NS5B polymerase inhibitor and a candidate drug evaluated for treatment of hepatitis C virus.</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>MK-8876 is an Inhibitor of HCV NS5B Site D.</p>

<p>KL-50, a selective toxin, effectively targets tumors deficient in the DNA repair protein O6-methylguanine-DNA-methyltransferase (MGMT), which corrects O6-alkylguanine lesions. This compound induces both DNA damage response pathways and cell cycle arrest in MGMT-deficient cells, regardless of mismatch repair (MMR) status. KL-50 shows promise in the study of brain tumors lacking MGMT.</p>

<p>A 76889 is an inhibitor of HIV-1 protease.</p>

<p>Ambelline has antitumor activity.</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>

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

<p>Cetefloxacin (E 4868) is a broad-spectrum antibacterial antibiotic with a minimum inhibitory concentration (MIC) ranging from 0.007 to 8 µg/ml. In mice, cetefloxacin demonstrates favorable pharmacokinetic properties and provides protection against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.</p>

<p>Menoctone is an orally effective antimalarial agent that inhibits blood-induced rodent malaria. It enhances the antimalarial effects of chloroquine or quinine, making it useful for malaria research.</p>

<p>LasR antagonist 1 (Compound 7), with an IC50 of 0.4 μM, is an effective antagonist of LasR that modulates quorum sensing (QS) in the opportunistic pathogen Pseudomonas aeruginosa [1].</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>UNC0638 hydrate selectively inhibits G9a and GLP histone methyltransferases with IC50 values of 15 nM and 19 nM, respectively. It is effective in inhibiting invasion and migration of TNBC cells in vitro. Additionally, UNC0638 hydrate acts as an inhibitor of EHMT1/2 and induces the expression of fetal hemoglobin (HbF) in cultures of human erythroid progenitor cells. Furthermore, it exhibits antiviral activity against FMDV (foot-and-mouth disease virus) and VSV (vesicular stomatitis virus), demonstrating remarkable potency and selectivity across various epigenetic and non-epigenetic targets.</p>

<p>SARS-CoV-2 Mpro-IN-32 (Compound 1) is a selective inhibitor of SARS-CoV-2 MPro with an IC50 value of 230 nM. In vitro, it also inhibits the replication of various SARS-CoV-2 variants.</p>

<p>Insecticidal agent 16 (compound A21) exhibits insecticidal activity against Plutella xylostella, with LC50 values of 1.2 and 13.2 µg/mL respectively.</p>

<p>SARS-CoV-2 Mpro-IN-28 (Compound 1K) is an inhibitor of SARS-CoV-2 Mpro, exhibiting an EC50 of 24 μM.</p>

<p>NNRT-IN-5 (compound 10d) is an orally available non-nucleoside reverse transcriptase (Reverse Transcriptase) inhibitor.</p>

<p>Neuraminidase-IN-18 (compound N5), a novel polyheterocyclic neuraminidase (NA) inhibitor, demonstrates significant inhibitory activity against H5N1 NA, with an IC 50 of 0.14 μM against the wild-type H5N1 NA and 0.27 μM against the H5N1-H274Y mutant NA. This compound effectively binds to NAs, inhibiting influenza virus replication at the cellular level [1].</p>

<p>N-Cbz-L-Cysteine (Cbz-cysteine) (compound 5) functions as a potent inhibitor of β-lactamase II, exhibiting a K i value of 97 µM [1].</p>

<p>SHEN26 (ATY014) is a potent, orally active RdRp inhibitor with an IC50 of 1.36 μM for SARS-CoV-2. As a 5'-cyclohexanecarboxylate derivative of GS-441524, SHEN26 inhibits viral nucleic acid synthesis, achieving antiviral effects. SHEN26 can be used for COVID-19 research [1] [2].</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>

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