e-2020

Donepezil HCl(Aricept) is a selective and effective AChE inhibitor for bAChE and hAChE (IC50: 8.12 11.6 nM).

Donepezil (Aricept) is a piperidine-based, potent, specific, and reversible inhibitor of acetylcholinesterase (AChE). It can be used for the treatment of mild to moderate dementia of the Alzheimer's type.

Myceliothermophin E is a polyketide-amino acid hybrid fungal metabolite that has been found inT. thermophilusand has anticancer and antimicrobial activities.1,2It is cytotoxic to DLD-1, Hep3B, HepG2, and HGC-27 cancer cells (IC50s = 0.32, 0.42, 0.26, and 0.08 μg/ml, respectively).1Myceliothermophin E is active against methicillin-resistant, but not -sensitive,S. aureus(MICs = 15.8 and >100 μM, respectively).2 1.Gao, Y.-L., Zhang, M.-L., Wang, X., et al.Isolation and characterization of a new cytotoxic polyketide-amino acid hybrid from Thermothelomyces thermophilus ATCC 42464Nat. Prod. Res.Epub ahead of print(2019) 2.Wang, X., Zhao, L., Liu, C., et al.New tetramic acids comprising of decalin and pyridones from Chaetomium olivaceum SD-80A with antimicrobial activityFront. Microbiol.102958(2020)

Resolvin E2 (RvE2) is a member of the specialized pro-resolving mediator (SPM) family of bioactive lipids.1It is produced from eicosapentaenoic acidviaan 18-HEPE intermediate, which is formed by aspirin-acetylated COX-2-mediated oxidation of EPA, by 5-lipoxygenase (5-LO) in human polymorphonuclear (PMN) neutrophils.2,3RvE2 (20 ng/animal) inhibits increases in inflammatory exudate neutrophil infiltration in a mouse model of peritonitis induced by zymosan A .3Hepatic RvE2 levels are increased in mice fed normal chow, as well as in a mouse model of high-fat diet-induced non-alcoholic fatty liver disease (NAFLD), by dietary supplementation with EPA.4Plasma levels of RvE2 are increased by dietary supplementation with fish oil containing ω-3 polyunsaturated fatty acids (PUFAs) in patients with peripheral artery disease or chronic kidney disease.1,5,6 1.Chiang, N., and Serhan, C.N.Specialized pro-resolving mediator network: An update on production and actionsEssays Biochem.64(3)443-462(2020) 2.Tjonahen, E., Oh, S.F., Siegelman, J., et al.Resolvin E2: Identification and anti-inflammatory actions: Pivotal role of human 5-lipoxygenase in resolvin E series biosynthesisChemistry & Biology131193-1202(2006) 3.Sungwhan, F.O., Pillai, P.S., Recchiuti, A., et al.Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammationJ. Clin. Invest.121(2)569-581(2011) 4.Echeverría, F., Valenzuela, R., Espinosa, A., et al.Reduction of high-fat diet-induced liver proinflammatory state by eicosapentaenoic acid plus hydroxytyrosol supplementation: Involvement of resolvins RvE1/2 and RvD1/2J. Nutr. Biochem.6335-43(2019) 5.Ramirez, J.L., Gasper, W.J., Khetani, S.A., et al.Fish oil increases specialized pro-resolving lipid mediators in PAD (the OMEGA-PAD II trial)J. Surg. Res.238164-174(2019) 6.Barden, A.E., Shinde, S., Burke, V., et al.The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney diseaseProstaglandins Other Lipid Mediat.1361-8(2018)

Conglobatin B is a bacterial metabolite that has been found inStreptomycesMST-91080 and has anticancer activity.1It is cytotoxic to NS-1 mouse myeloma cells (IC50= 0.084 μg/ml) but not NFF human fibroblasts (IC50= >100 μg/ml). 1.Lacey, H.J., Booth, T.J., Vuong, D., et al.Conglobatins B-E: Cytotoxic analogues of the C2-symmetric macrodiolide conglobatinJ. Antibiot. (Tokyo)73(11)756-765(2020)

Conglobatin C1 is a bacterial metabolite that has been found inStreptomycesMST-91080 and has anticancer activity.1It is cytotoxic to NS-1 mouse myeloma cells (IC50= 1.05 μg/ml) but not NFF human fibroblasts (IC50= >100 μg/ml). 1.Lacey, H.J., Booth, T.J., Vuong, D., et al.Conglobatins B-E: Cytotoxic analogues of the C2-symmetric macrodiolide conglobatinJ. Antibiot. (Tokyo)73(11)756-765(2020)

9(S),12(S),13(S)-TriHOME is a linoleic acid-derived oxylipin that has diverse biological activities.1,2,3,4It has been found in various plants and is produced in human eosinophils in a 15-lipoxygenase-dependent, soluble epoxide hydrolase-independent manner.1,59(S),12(S)13(S)-TriHOME inhibits antigen-induced β-hexosaminidase release from RBL-2H3 mast cells (IC50= 28.7 μg ml).2It inhibits LPS-induced nitric oxide (NO) production in BV-2 microglia (IC50= 40.95 μM).3In vivo, 9(S),12(S),13(S)-TriHOME (1 g animal) enhances the antiviral IgA and IgG antibody responses induced by a nasal influenza hemagglutinin (HA) vaccine by 5.2- and 2-fold, respectively, in mice.4 1.Hamberg, M., and Hamberg, G.Peroxygenase-catalyzed fatty acid epoxidation in cereal seeds: Sequential oxidation of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)-octadecenoic acidPlant Physiol.110(3)807-815(1996) 2.Hong, S.S., and Oh, J.S.Inhibitors of antigen-induced degranulation of RBL-2H3 cells isolated from wheat branJ. Korean Soc. Appl. Biol. Chem.5569-74(2012) 3.Kim, C.S., Kwon, O.W., Kim, S.Y., et al.Five new oxylipins from Chaenomeles sinensisLipids49(11)1151-1159(2014) 4.Shirahata, T., Sunazuka, T., Yoshida, K., et al.Total synthesis, elucidation of absolute stereochemistry, and adjuvant activity of trihydroxy fatty acidsTetrahedron62(40)9483-9496(2006) 5.Fuchs, D., Tang, X., Johnsson, A.-K., et al.Eosinophils synthesize trihydroxyoctadecenoic acids (TriHOMEs) via a 15-lipoxygenase dependent processBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(4)158611(2020)

N-(4-Aminobenzoyl)-L-glutamic acid is an oxidation product and a metabolite of tetrahydrofolate.1Levels of N-(4-aminobenzoyl)-L-glutamic acid are increased in the plasma of mice fed a high folic acid-containing diet.2 1.Reed, L.S., and Archer, M.C.Oxidation of tetrahydrofolic acid by airJ. Agric. Food Chem.28(4)801-805(1980) 2.Burton, M.A., Antoun, E., Penailillo, R.S., et al.Folic acid induces intake-related changes in the mammary tissue transcriptome of C57BL/6 miceNutrients12(9)2821(2020)

Tunicamycin 15:1 is a mixture of tunicamycin structural isomers that contain a 15-carbon N-acyl chain with variable branching patterns. The N-acyl chain incorporated into tunicamycins, like tunicamycin 15:1, is derived from the same pool of cellular branched-chain fatty acids (BCFAs) inStreptomycesand directly impacts the biological activity of each individual tunicamycin variant.1,2,3Purified tunicamycin 15:1 withiso,anteiso, or a mixture ofisoandanteisobranching configurations inhibit bacterial phospho-MurNAc-pentapeptide transferase (MraY) with IC50values of 0.05, 0.36, and 0.09 μM, respectively.2 1.Price, N.P.J., Jackson, M.A., Hartman, T.M., et al.Branched chain lipid metabolism as a determinant of the N-Acyl variation of Streptomyces natural productsACS Chem. Biol.16(1)116-124(2021) 2.Hering, J., Dunevall, E., Snijder, A., et al.Exploring the active site of the antibacterial target MraY by modified tunicamycinsACS Chem Biol.15(11)2885-2895(2020) 3.Duksin, D., and Mahoney, W.C.Relationship of the structure and biological activity of the natural homologues of tunicamycinJ. Biol. Chem.257(6)3105-3109(1982)

Tunicamycin 17:1 is a mixture of tunicamycin structural isomers that contain a 17-carbon N-acyl chain with variable branching patterns. The N-acyl chain incorporated into tunicamycins, like tunicamycin 17:1, is derived from the same pool of cellular branched-chain fatty acids (BCFAs) inStreptomycesand directly impacts the biological activity of each individual tunicamycin variant.1,2,3Purified tunicamycin 17:1 withisooranteisobranching configurations inhibits bacterial phospho-MurNAc-pentapeptide transferase (MraY) with IC50values of 0.12 and 0.9 μM, respectively.2 1.Price, N.P.J., Jackson, M.A., Hartman, T.M., et al.Branched chain lipid metabolism as a determinant of the N-Acyl variation of Streptomyces natural productsACS Chem. Biol.16(1)116-124(2021) 2.Hering, J., Dunevall, E., Snijder, A., et al.Exploring the active site of the antibacterial target MraY by modified tunicamycinsACS Chem Biol.15(11)2885-2895(2020) 3.Duksin, D., and Mahoney, W.C.Relationship of the structure and biological activity of the natural homologues of tunicamycinJ. Biol. Chem.257(6)3105-3109(1982)

Ribavirin-13C5is intended for use as an internal standard for the quantification of ribavirin by GC- or LC-MS. Ribavirin is an antiviral guanosine nucleoside analog.1,2Upon entry into cells, ribavirin is metabolized to an active triphosphate form that induces viral RNA chain termination and inhibits viral polymerases. It reduces replication in a panel of seven RNA and four DNA viruses in Vero cells (EC50s = 2-95 μg/ml).3Ribavirin also reduces replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Vero cells (EC50= 109.5 μM).4Aerosol administration of ribavirin (30 mg/kg) reduces mortality in a mouse model of influenza A infection.5Formulations containing ribavirin have been used in the treatment of respiratory syncytial virus (RSV), hepatitis C virus (HCV), and viral hemorrhagic fevers. 1.Gilbert, B.E., and Knight, V.Biochemistry and clinical applications of ribavirinAntimicrob. Agents Chemother.30(2)201-205(1986) 2.Gordon, C.J., Tchesnokov, E.P., Woolner, E., et al.Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potencyJ. Biol. Chem.295(20)6785-6797(2020) 3.Kirsi, J.J., North, J.A., McKernan, P.A., et al.Broad-spectrum antiviral activity of 2-β-D-ribofuranosylselenazole-4-carboxamide, a new antiviral agentAntimicrob. Agents Chemother.24(3)353-361(1983) 4.Wang, M., Cao, R., Zhang, L., et al.Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitroCell Res.30(3)269-271(2020) 5.Wilson, S.Z., Knight, V., Wyde, P.R., et al.Amantadine and ribavirin aerosol treatment of influenza A and B infection in miceAntimicrob. Agents Chemother.17(4)642-648(1980)