Microbiologia/Virologia

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

<p>WRN inhibitor 11 (Example 17) is an orally effective inhibitor of WRN helicase, with an IC50 of 63 nM.</p>

SARS-CoV-2-IN-100 (Compound 172) is a broad-spectrum antiviral agent against various SARS-CoV-2 variants. It works synergistically with Nirmatrelvir to reduce the risk of antiviral resistance.

<p>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.</p>

<p>SARS-CoV-2 Mpro-IN-31 (Compound 18) is an inhibitor of SARS-CoV-2 MPro with an IC50 of 11 nM. Additionally, this compound effectively inhibits the enzymatic activity of the cysteine proteases cathepsin B and cathepsin L, with IC50 values of 24 nM and 1.8 nM, respectively.</p>

<p>SARS-CoV-2-IN-102 (example 58) is an inhibitor of the SARS-CoV papain-like protease (SARS-CoVPLpro), demonstrating an IC50 of less than 100 nM.</p>

<p>Antifungalagent 113 (compound 9a) serves as an effective antifungal and antibacterial agent. It exhibits strong inhibitory activity against both S. aureus and methicillin-resistant S. aureus.</p>

<p>HRSV/HMPV-IN-1 (compound 3) is an inhibitor targeting HRSV/HMPV, exhibiting EC50 values of &lt; 0.2 μM against human RSV-A and &lt; 0.5 μM for human MPV A2 TN/94-49. This compound is utilized in the study of bronchiolitis and pneumonia.</p>

<p>MED6-189, an analog of kalihinol, disrupts the apicoplast functions and vesicular transport in the malignant malaria parasite (P. falciparum, IC50 &lt; 50 nM). The compound specifically targets the apicoplast, which is a non-photosynthetic plastid essential for isoprenoid synthesis, found in most apicomplexan parasites.</p>

<p>Polθ-IN-5 (Compound 139) is an inhibitor of DNA polymerase theta (Polθ) that exhibits antitumor activity.</p>

<p>Ipronidazole (RO-71554) is an orally effective antiprotozoal agent used to prevent and ameliorate histomoniasis in turkeys, commonly referred to as blackhead disease.</p>

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

<p>Neuraminidase-IN-4 inhibits neuraminidase (EC50: 1.59 μM) and has strong anti-H5N1 activity.</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>Enpatoran hydrochloride (M5049 hydrochloride) is a TLR7/8 inhibitor with antiviral activity that is used in the study of autoimmune diseases.</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>RAD51-IN-8 inhibits RAD51-BRCA2 interaction and H4A4 with EC50 of 19 μM; a micromolar PPI inhibitor.</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>Ro 24-4383 is a carbamate-linked dual-action antibacterial agent.</p>

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

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

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