p 32

Oxanosine is an analog of guanosine that has been found in S. capreolus and has diverse biological activities, including antibacterial, antiviral, and anticancer properties. It is active against a variety of bacteria, including S. flexneri, P. mirabilis, and E. coli (MICs = 6.25, 12.5, 25 µg/ml, respectively, on peptone, but not nutrient, agar). Oxanosine inhibits replication of the HIV-1 strain IIIb in infected CEM and U937, but not H9, cells (EC50s = 7, 27, and >500 µg/ml, respectively). It also inhibits the growth of HeLa human cervical cancer cells (IC50 = 32 µg/ml) and reduces tumor growth in a murine L1210 lymphocytic leukemia model.

Antibacterial Agent 128, a siderophore analog-Ciprofloxacin (Ciprofloxacin) conjugate connected via a cleavable linker, demonstrates effective antibiotic properties. Specifically, it exhibits activity against P. aeruginosa and B. pseudomallei, with Minimum Inhibitory Concentration (MIC) values ranging from 0.25 to 64 μg/mL and 1 to 32 μg/mL, respectively [1].

Lynronne-1, an antimicrobial peptide, exhibits activity against Gram-positive bacteria, including multi-drug resistant (MDR) strains, with a minimal inhibitory concentration (MIC) of 8-32 μg/mL for methicillin-resistant MRSA strains. Additionally, it effectively reduces the bacterial load in a murine model of MRSA-infected wounds and demonstrates efficacy against P. aeruginosa infections [1].

Averantin exhibits antifungal activity against Fusariumsolani, pathogenic fungus of P. notoginseng, with minimum inhibitory concentrations (MICs) of 16-32 ug/mL, and shows antibacterial activity against Bacillussubtilis with MICs of 16-32 ug/mL.

Beauvericin A is a cyclodepsipeptide and derivative of beauvericin originally isolated fromB. bassianathat has diverse biological activities.1,2,3It is active againstM. tuberculosis(MIC = 25 μg/ml) andP. falciparum(IC50= 12 μg/ml).2Beauvericin A is toxic to brine shrimp (LD100= 32 μg/ml).3 1.Gupta, S., Montillor, C., and Hwang, Y.-S.Isolation of Novel Beauvericin Analogues from the Fungus Beauveria bassianaJ. Nat. Prod.58(5)733-738(1995) 2.Nilanonta, C., Isaka, M., Kittakoop, P., et al.Antimycobacterial and antiplasmodial cyclodepsipeptides from the insect pathogenic fungus Paecilomyces tenuipes BCC 1614Planta Med.66(8)756-758(2000) 3.Shi, S., Li, Y., Ming, Y., et al.Biological activity and chemical composition of the endophytic fungus Fusarium sp. TP-G1 obtained from the root of Dendrobium officinale Kimura et MigoRec. Nat. Prod.12(6)549-556(2018)

Purfalcamine is an orally active, selective Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) inhibitor with an IC50 of 17 nM and an EC50 of 230 nM, exhibiting antimalarial activity by inducing developmental arrest of malaria parasites at the schizont stage[1][2].

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).

DCVC inhibits pathogen-stimulated TNF-α in human extra placental membranes in vitro.Target: TNF-αin vitro: DCVC inhibits pathogen stimulated cytokine release from tissue punch cultures. DCVC (5-50 μM) significantly inhibits LTA-, LPS-, and GBS-stimulated cytokine release from tissue cultures as early as 4 h (P ≤ 0.05). In contrast, TCA (up to 500 μM) does not inhibit LTA-stimulated cytokine release from tissue punches. DCVC effects on LTA-stimulated and LPS-stimulated TNF-α release from tissue punch cultures of extraplacental membranes. DCVC effects on GBS-stimulated release of pro-inflammatory cytokines from extraplacental membranes in transwell cultures. [1]. Boldenow E, et al. The trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine but not trichloroacetate inhibits pathogen-stimulated TNF-α in human extraplacental membranes in vitro. Reprod Toxicol. 2015 Apr;52:1-6. [2]. Lash LH, et al. Multigenerational study of chemically induced cytotoxicity and proliferation in cultures of human proximal tubular cells. Int J Mol Sci. 2014 Nov 18;15(11):21348-65. [3]. Yoo HS, et al. Comparative analysis of the relationship between trichloroethylene metabolism and tissue-specific toxicity among inbred mouse strains: kidney effects. J Toxicol Environ Health A. 2015;78(1):32-49.

Lynronne-2, an antimicrobial peptide, exhibits activity against Gram-positive bacteria, including methicillin-resistant MRSA strains (MIC: 32-256 μg/mL), and demonstrates effectiveness in combating P. aeruginosa infections [1].

Ranalexin, an antimicrobial peptide, demonstrates inhibition of S. aureus, E. coli, and P. aeruginosa, with respective minimum inhibitory concentrations (MICs) of 4, 32, and 128 μg/mL [1].

p32 inhibitor M36 is an inhibitor of p32 mitochondrial protein. It binds directly to p32 and inhibits the p32 association with LyP-1.

Leoidin is a depsidone originally isolated from L. gangaleoides that has antibacterial and enzyme inhibitory activities.1,2,3 It is active against the bacteria E. faecalis, H. influenzae, M. catarrhalis, S. aureus, and S. pneumoniae (MICs = 8, 32, 1, 128, and 64 μg/ml, respectively).2 Leoidin inhibits phenylalanyl-tRNA synthetase (PheRS) isolated from P. aeruginosa (IC50 = 42 μM). It also inhibits organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3 with Ki values of 0.08 and 1.84 μM, respectively, in CHO cells expressing the human transporters.3

Previridicatumtoxin is a fungal metabolite that has been found inP. aethiopicumand has diverse biological activities.1,2It is an intermediate in the biosynthesis of the mycotoxin viridicatumtoxin . Previridicatumtoxin is active against methicillin-resistantS. aureus(MRSA) and vancomycin-resistantE. faecalis(IC50s = 4.4 and 4.8 μM, respectively), as well asC. albicansandS. cerevisiae(MIC = 32 μg/ml for both).2,1It is cytotoxic to NCI H460, KB-3-1, and SW620 cancer cells (IC50s = 5.3, 4.1, and 6 μM, respectively).2 1.Chooi, Y.H., Wang, P., Fang, J., et al.Discovery and characterization of a group of fungal polycyclic polyketide prenyltransferasesJ. Am. Chem. Soc.134(22)9428-9437(2012) 2.Shang, Z., Salim, A.A., Khalil, Z., et al.Viridicatumtoxins: Expanding on a rare tetracycline antibiotic scaffoldJ. Org. Chem.80(24)12501-12508(2015)

Anti-infective agent 2 (compound 3k) is an antiprotozoal and antimycobacterial agent. It exhibits antiparasitic activity against P. falciparum and T. brucei rhodesiense, with IC50 values of 0.07 and 2.20 μM, respectively, and shows antimycobacterial activity against Mycobacterium smegmatis with a MIC of 32 μg mL [1].

Milbemycin A4 oxime, a derivative of milbemycin A4 and a component of milbemycin oxime, exhibits insecticidal and nematocidal activity. At 0.05 mg kg, it reduces microfilariae of the heartworm D. immitis in naturally infested dogs and inhibits the growth of C. glabrata clinical isolates with MIC80 values of 16 to >32 μg ml. At 2.5 μg ml, it blocks fluconazole efflux from C. glabrata clinical isolates (but not from strains lacking CgCDR1 and PDH1 efflux pumps) and reduces MICs of fluconazole and 4-nitroquinoline 1-oxide in wild-type C. glabrata. Furthermore, it enhances adriamycin-induced inhibition of cell growth, increases intracellular accumulation of adriamycin and the P-glycoprotein substrate rhodamine 123 in adriamycin-resistant, but not adriamycin-sensitive, MCF-7 breast cancer cells in a concentration-dependent manner.

MraY-IN-3 (12a) is a potent inhibitor of bacterial translocase MraY with an IC50 of 140 μM and a concentration of 46 μg ml.

AZD-5672 is an antagonist of CCR5 with an IC50 of 0.32 nM. AZD-5672 inhibits hERG cardiac ion channel binding and P-gp-mediated digoxin transport with IC50s of 7.3 μM and 32 μM. AZD-5672 can be used in studies about rheumatoid arthritis.

Lynronne-3, an antimicrobial peptide, demonstrates activity against Gram-positive bacteria, including multi-drug resistant (MDR) strains, with a minimum inhibitory concentration (MIC) ranging from 32-128 μg/mL for methicillin-resistant Staphylococcus aureus (MRSA) strains. Additionally, Lynronne-3 is efficacious in combating Pseudomonas aeruginosa infections [1].

(32-Carbonyl)-RMC-5552 is a highly effective mTOR inhibitor, inhibiting both mTORC1 and mTORC2 substrate phosphorylation. It significantly suppresses the phosphorylation of p-P70S6K-(T389), p-4E-BP1-(T37 36), and p-AKT1 2 3-(S473) with pIC50 values >9, >9, and 8~9, respectively.

C18 D-threoCeramide (d18:1/18:0) is a synthetic ceramide and stereoisomer of C18 ceramide .1It inhibits rat brain mitochondrial ceramidase (mt-CDase) with an IC50value of 16.6 μM.2[Matreya, LLC. Catalog No. 1855] 1.Koolath, S., Murai, Y., Suga, Y., et al.Chiral combinatorial preparation and biological evaluation of unique ceramides for inhibition of sphingomyelin synthaseChirality32(3)308-313(2019) 2.Usta, J., El Bawab, S., Roddy, P., et al.Structural requirements of ceramide and sphingosine based inhibitors of mitochondrial ceramidaseBiochemistry40(32)9657-9668(2001)

Piericidin B is a bacterial metabolite that has been found inS. mobaraensisand has insecticidal and antimicrobial activities.1,2,3It inhibits NADH oxidase activity in isolated bovine heart mitochondria and inhibits respiration in isolated rat liver mitochondria and isolated cockroach (P. americana) muscle mitochondria.2,3Topical application of piericidin B (4 μg/insect) induces mortality in 87.5% of houseflies (M. domestica).1It induces 93.3, 100, and 100% mortality in rice stem borer (C. simples), silkworm (B. mori), and green caterpillar (P. rapae) larvae, respectively, when applied at respective concentrations of 60, 4.8, and 96 μg/larva. Piericidin B is active against the fungiT. asteroides,T. rubrum,M. gypseum, andC. neoforms(MICs = 20, 10, 20, and 2 μg/ml, respectively), as well as the bacteriaM. luteusandP. vulgaris(MICs = 50 and 100 μg/ml, respectively). 1.Takahashi, N., Suzuki, A., Kimura, Y., et al.Isolation, structure and physiological activities of piericidin B, natural Insecticide produced by a StreptomycesAgr. Biol. Chem.32(9)1115-1122(1968) 2.Jeng, M., Hall, C., Crane, F.L., et al.Inhibition of mitochondrial electron transport by piericidin A and related compoundsBiochemistry7(4)1311-1322(1968) 3.Mitsui, T., Fukami, J.-I., Fukunaga, K., et al.Studies on piericidin. I. : Effects of piericidin A and B on mitochondrial electron transport in insect muscle comparing with rotenoneSci. Insect Control34(3)126-134(1969)