mic-11

IMPDH2-IN-2 是一种肌苷 5'-单磷酸脱氢酶 (IMPDH) 抑制剂，具有抗菌活性和潜在的抗结核活性，可用于研究炎症和免疫功能异常。

DprE1-IN-11 (compound 3) 作为一种口服活性DprE1抑制剂，针对 MTB H37Rv 和 MDR-MTB 菌株显示出有效的抗结核活性，其最小抑菌浓度 (MIC) 范围为 <0.029-0.095 μM。

Carbonic Anhydrase Inhibitor28 (Compound 11) 作为一种有效的Pseudomonas aeruginosa碳酸酐酶抑制剂，展现出良好的抑菌活性。具体来说，其对P. aeruginosa 的最小抑菌浓度(MIC)为0.5 μg mL，最小杀菌浓度(MBC)为1 μg mL。因此，Carbonic Anhydrase Inhibitor28 在抗感染研究领域具有潜在应用价值。

Antibiofilm agent-14 (compound 11) 是一种抗膜剂，对 C.albicans SC5314 具有抗真菌活性，MIC 值为 50 μM。

DNA Gyrase-IN-15 (Compound 11) 是一种抗菌剂，同时也是DHPS和DNA gyrase的抑制剂，其IC50分别为1.73 µM和0.07 µM。它对粪肠球菌（MIC为15.62 µg mL）、鲍曼不动杆菌、肠杆菌（MIC为7.81 µg mL）、铜绿假单胞菌、肺炎克雷伯菌和金黄色葡萄球菌表现出抗菌活性。此外，DNA Gyrase-IN-15 对粪肠球菌也具有抗生物膜活性。

Benastatin A is a polyketide synthase-derived benastatin that has been found inStreptomycesand has diverse biological activities.1,2,3It inhibits glutathione S-transferase (GST; Ki= 5 μM for the rat liver enzyme).2Benastatin A is active against several bacteria, including methicillin-resistantS. aureus(MRSA; MIC = 3.12 μg ml). It induces apoptosis and cell cycle arrest at the G1 G0phase in Colon 26 mouse colon cancer cells when used at concentrations of 20 and 16 μM, respectively.3 1.Xu, Z., Schenk, A., and Hertweck, C.Molecular analysis of the benastatin biosynthetic pathway and genetic engineering of altered fatty acid-polyketide hybridsJ. Am. Chem. Soc.129(18)6022-6030(2007) 2.Aoyagi, T., Aoyama, T., Kojima, F., et al.Benastatins A and B, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. I. Taxonomy, production, isolation, physico-chemical properties and biological activitiesJ. Antibiot. (Tokyo)45(9)1385-1390(1992) 3.Kakizaki, I., Ookawa, K., Ishikawa, T., et al.Induction of apoptosis and cell cycle arrest in mouse colon 26 cells by benastatin AJpn. J. Cancer Res.91(11)1161-1168(2000)

3-Hydroxyterphenyllin is a p-terphenyl fungal metabolite originally isolated from A. candidus that has diverse biological activities, including antioxidant, antiproliferative, antibacterial, and antiviral properties.1,2,3,4 It has a 96% scavenging effect on 2,2-diphenyl-1-picrylhydrazyl radicals when used at a concentration of 100 μg/ml.2 3-Hydroxyterphenyllin inhibits the growth of HeLa cervical, A549 lung, and HepG2 liver cancer cells (IC50s = 23, 36, and 32 μM, respectively), as well as methicillin-resistant S. aureus (MRSA) and V. vulnificus bacteria (MIC = 31 μg/ml for both).3 It also inhibits HIV-1 integrase in both coupled and strand transfer assays (IC50s = 2.8 and 12.1 μM, respectively).4References1. Kurobane, I., Vining, L.C., McInnes, A.G., et al. 3-Hydroxyterphenyllin, a new metabolite of Aspergillus candidus. Structure elucidation by 1H and 13C nuclear magnetic resonance spectroscopy. J. Antibiot. (Tokyo) 32(6), 559-564 (1979).2. Yen, G.-C., Chang, Y.-C., Sheu, F., et al. Isolation and characterization of antioxidant compounds from Aspergillus candidus broth filtrate. J. Agric. Food Chem. 49(3), 1426-1431 (2001).3. Wang, W., Liao, Y., Tang, C., et al. Cytotoxic and antibacterial compounds from the coral-derived fungus Aspergillus tritici SP2-8-1. Mar. Drugs 15(11), E348 (2017).4. Singh, S.B., Jayasuriya, H., Dewey, R., et al. Isolation, structure, and HIV-1-integrase inhibitory activity of structurally diverse fungal metabolites. J. Ind. Microbiol. Biotechnol. 30(12), 721-731 (2003). 3-Hydroxyterphenyllin is a p-terphenyl fungal metabolite originally isolated from A. candidus that has diverse biological activities, including antioxidant, antiproliferative, antibacterial, and antiviral properties.1,2,3,4 It has a 96% scavenging effect on 2,2-diphenyl-1-picrylhydrazyl radicals when used at a concentration of 100 μg/ml.2 3-Hydroxyterphenyllin inhibits the growth of HeLa cervical, A549 lung, and HepG2 liver cancer cells (IC50s = 23, 36, and 32 μM, respectively), as well as methicillin-resistant S. aureus (MRSA) and V. vulnificus bacteria (MIC = 31 μg/ml for both).3 It also inhibits HIV-1 integrase in both coupled and strand transfer assays (IC50s = 2.8 and 12.1 μM, respectively).4 References1. Kurobane, I., Vining, L.C., McInnes, A.G., et al. 3-Hydroxyterphenyllin, a new metabolite of Aspergillus candidus. Structure elucidation by 1H and 13C nuclear magnetic resonance spectroscopy. J. Antibiot. (Tokyo) 32(6), 559-564 (1979).2. Yen, G.-C., Chang, Y.-C., Sheu, F., et al. Isolation and characterization of antioxidant compounds from Aspergillus candidus broth filtrate. J. Agric. Food Chem. 49(3), 1426-1431 (2001).3. Wang, W., Liao, Y., Tang, C., et al. Cytotoxic and antibacterial compounds from the coral-derived fungus Aspergillus tritici SP2-8-1. Mar. Drugs 15(11), E348 (2017).4. Singh, S.B., Jayasuriya, H., Dewey, R., et al. Isolation, structure, and HIV-1-integrase inhibitory activity of structurally diverse fungal metabolites. J. Ind. Microbiol. Biotechnol. 30(12), 721-731 (2003).

Linearmycin A is a polyene antibiotic that has been found inStreptomyces.1It is active against the bacteriaS. aureusandE. coli(MICs = 3.1 and 1.6 μg disc, respectively), the fungiS. cerevisiaeandC. albicans(MICs = 0.1 and 1.6 μg disc, respectively), and the plant pathogenic fungusA. nigerin disc assays (MIC = 0.2 μg disc). Linearmycin A induces lysis and degradation ofB. subtilisas a component ofStreptomycesMg1 extract.2 1.Sakuda, S., Guce-Bigol, U., Itoh, M., et al.Novel linear polyene antibiotics: LinearmycinsJ. Chem. Soc., Perkin Trans. 1182315-2319(1996) 2.Stubbendieck, R.M., and Straight, P.D.Escape from lethal bacterial competition through coupled activation of antibiotic resistance and a mobilized subpopulationPLoS Genet.11(12)e1005722(2015)

TunR1 is an antibiotic and derivative of tunicamycin .1It is active againstB. subtilis(MIC = 0.3 μg ml) and increases the efficacy of the β-lactam antibiotics oxacillin , methicillin , and penicillin G againstB. subtiliswhen used at a concentration of 0.4 μg ml. TunR1 (5 μg ml) is cytotoxic to MDA-MB-231 breast cancer cells and non-cancerous CHO cells. Unlike tunicamycin, TunR1 does not inhibit glycosylation in a protein N-glycosylation assay. 1.Price, N.P., Hartman, T.M., Li, J., et al.Modified tunicamycins with reduced eukaryotic toxicity that enhance the antibacterial activity of β-lactamsJ. Antibiot. (Tokyo)70(11)1070-1077(2017)

TunR2 is an antibiotic and derivative of tunicamycin .1It is active againstB. subtilis(MIC = 0.3 μg ml) and increases the efficacy of the β-lactam antibiotics oxacillin , methicillin , and penicillin G againstB. subtiliswhen used at a concentration of 0.4 μg ml. Unlike tunicamycin, TunR2 is non-toxic toS. cerevisiae(MIC = >10 μg ml) and does not inhibit glycosylation in a protein N-glycosylation assay. TunR2 also has reduced antiproliferative activity against MDA-MB-231 and CHO cells compared with tunicamycin. 1.Price, N.P., Hartman, T.M., Li, J., et al.Modified tunicamycins with reduced eukaryotic toxicity that enhance the antibacterial activity of β-lactamsJ. Antibiot. (Tokyo)70(11)1070-1077(2017)

Kocurin is a thiazolyl peptide originally isolated fromK. palustrisand has antibiotic activity.1It is active against methicillin-resistantS. aureus(MRSA; MIC = 0.25 μg ml), as well asB. subtilisandE. faeciumin a solid agar test when used at a concentration of 8 μg ml. Kocurin is also active againstE. faecium,E. faecalis,S. epidermidis, and clinical isolates of vancomycin-resistant enterococci (MICs = 0.004-1.025 μg ml).2In vivo, kocurin (2.5, 5, and 10 mg ml) increases survival in a mouse model ofE. faecium-induced septicemia. It decreases the number of colony forming units (CFUs) in a mouse model of MRSA lung infection. 1.Martin, J., da S. Sousa, T., Crespo, G., et al.Kocurin, the true structure of PM181104, an anti-methicillin-resistant Staphylococcus aureus (MRSA) thiazolyl peptide from the marine-derived bacterium Kocuria palustrisMar. Drugs11(2)387-398(2013) 2.Mahajan, G., Thomas, B., Parab, R., et al.In vitro and in vivo activities of antibiotic PM181104Antimicrob. Agents Chemother.57(11)5315-5319(2013)

Aquastatin A is a fungal metabolite originally isolated fromF. aquaeductuumthat has diverse biological activities.1It is active againstS. aureus(MIC = 32 μg/ml) and inhibits enoyl-acyl carrier protein reductase (Fabl; IC50= 3.2 μM) andS. aureusfatty acid synthesis (IC50= 3.5 μM).2Aquastatin A also inhibits the Na+/K+-ATPase and H+/K+-ATPase (IC50s = 7.1 and 6.2 μM, respectively), as well as protein tyrosine phosphatase 1B (PTP1B; IC50= 0.19 μM).1,3 1.Hamano, K., Kinoshita-Okami, M., Minagawa, K., et al.Aquastatin A, an inhibitor of mammalian adenosine triphosphatases from Fusarium aquaeductuum. Taxonomy, fermentation, isolation, structure determination and biological propertiesJ. Antibiot. (Tokyo)46(11)1648-1657(1993) 2.Kwon, Y.-J., Fang, Y., Xu, G.-H., et al.Aquastatin A, a new inhibitor of enoyl-acyl carrier protein reductase from Sporothrix sp. FN611Biol. Pharm. Bull.32(12)2061-2064(2009) 3.Seo, C., Soh, J.H., Oh, H., et al.Isolation of the protein tyrosine phosphatase 1B inhibitory metabolite from the marine-derived fungus Cosmospora sp. SF-5060Bioorg. Med. Chem. Lett.19(21)6095-6097(2009)

Anti-inflammatory agent 11 (化合物 16) 是有效的抗结核分枝杆菌剂，可用于结核病(TB)的研究。Anti-inflammatory agent 11 抑制Mtb H37Rv 和M299的生长，MIC50分别为 1.3 和 6.9 μM。Anti-inflammatory agent 11 也是一种抗炎剂，通过抑制 iNOS 的表达抑制NO，同时抑制 TNF-α 和 IL-1β 的产生。

Antitubercular agent-11 (Compound 1e) 是一种具有较大供电子基团 (Bu-t)的抗结核剂，其 MIC 值为 0.060 μg mL。

Anticancer agent 36 (compound 11) 是一种有效的抗微生物剂和抗癌剂，是一种磺酰脲类衍生物。Anticancer agent 36 对蕈状芽孢杆菌、大肠杆菌和白色念珠菌的微生物生长有抑制作用 (MIC: 0.156 - 0.039 mg mL)。Anticancer agent 36 能够抑制 A549 细胞 (IC50: 19.7 μg mL)、PC3 细胞 (IC50: 11.9 μg mL) 生长。

11-Keto fusidic acid 对金黄色葡萄球菌具有较强的抗菌活性，MIC 值为0.078μg mL。

(22S,24E)-3β,22-Diacetoxylanosta-7,9(11),24-trien-26-oic acid (compound 15) 为具有抗结核活性的化合物，对结核分枝杆H37Ra的最小抑菌浓度（MIC）为12.5 μg mL，并展现出对Vero细胞的细胞毒性，其半数抑制浓度（IC50）值为32 μM[1]。

Antifungalagent 48 (Example 112)是一种针对Cryptococcus neoformans的抗真菌剂，展现出MIC为11 μM的抗菌活性。

PptT-IN-4 (Compound 3a) 为PptT抑制剂，IC50为0.71 μM。其对MtbH37Rv的MIC值为42 μM，并且还能抑制hERG、hCav1.2和hNav1.5通道，对应IC50s分别为11 μM、8.1 μM、6.9 μM。

InhA-IN-7（Compound 11）作为Triclocan衍生物，对烯酰基载体蛋白还原酶（InhA）显示出较强的抑制效果，其IC50为96 nM。此化合物能有效抑制Mycobacterium tuberculosis的野生型及突变株增殖，其MIC值介于19至75 μM之间。

DNA Gyrase-IN-11 (Compound 23Be) 是一种抑制蛋白质合成 (IC50为 0.74 μM) 和 DNA 复制的化合物。该化合物通过抑制 DNA Gyrase（一种能够抑制大肠杆菌E. coli的 DNA 超螺旋形成的酶），IC50为 11.9 μM，从而发挥作用。此外，DNA Gyrase-IN-11 还显示出针对 Streptococcus pneumoniae、Streptococcus pyogenes、Haemophilus influenzae 和 Staphylococcus aureus 的抗菌活性，其最小抑菌浓度（MIC）范围为 0.008-0.25 μg mL。

Mycobacterium Tuberculosis-IN-5 (Compound 11),作为5-Fluoroindole的盐酸盐形式,具有显著的抗菌功能,能够抑制Mycobacterium tuberculosis,其MIC值达到29.1 μM.此化合物在大鼠肝微粒体中显示良好的代谢稳定性,并且在小鼠体内展示出抗结核活性.