2-Deacetoxydecinnamoyltaxinine J is a natural product from Taxus cuspidta Sibe et Zucc.

2-Deacetoxytaxinine J shows significant in vitro activity against breast cancer cell line at a concentration of 20 microM and 10 microM in MCF-7 and MDA-MB-231 respectively.

Trypacidin is a fungal metabolite originally isolated fromA. fumigatus.1It is active againstB. subtilisandM. bovis(MICs = 12.5 and 1.25 μg/ml, respectively), as well asT. cruziandT. gondii(MICs = 5-10 and 10-20 μg/ml, respectively).1,2It reduces viability and induces lysis of A549 human lung cancer cells (IC50s = 7.4 μM for both).3Trypacidin increases survival in a mouse model ofT. gondiiinfection when administered in six doses of 12.5 mg/kg each.1 1.Balan, J., Ebringer, L., Nemec, P., et al.Antiprotozoal antibiotics. II. Isolation and characterization of trypacidin, a new antibiotic, active against Trypanosoma cruzi and Toxoplasma gondiiJ. Antibiot. (Tokyo)16157-160(1963) 2.Song, Z., Liu, Y., Gao, J., et al.Antitubercular metabolites from the marine-derived fungus strain Aspergillus fumigatus MF029Nat. Prod. Res.1-8(2019) 3.Gauthier, T., Wang, X., Dos Santos, J.S., et al.Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cellsPLoS One7(2)e29906(2012)

Stephacidin B is a fungal metabolite that has been found inA. ochraceus.1Dimeric stephacidin B is rapidly converted to a monomer, avrainvillamide ,in vitro.2Stephacidin B is cytotoxic to a variety of cancer cells, including testosterone-independent PC3 and -sensitive LNCaP prostate cancer cells (IC50s = 0.37 and 0.06 μM, respectively) and estradiol-independent SK-BR-3 and -sensitive MCF-7 breast cancer cells (IC50s = 0.32 and 0.27 μM, respectively).1It induces apoptosis in HepG2 and Huh7 hepatocellular carcinoma cells when used at a concentration of 4 μM.3 1.Qian-Cutrone, J., Huang, S., Shu, Y.-Z., et al.Stephacidin A and B: Two structurally novel, selective inhibitors of the testosterone-dependent prostate LNCaP cellsJ. Am. Chem. Soc.124(49)14556-14557(2002) 2.Wulff, J.E., Herzon, S.B., Siegrist, R., et al.Evidence for the rapid conversion of stephacidin B into the electrophilic monomer avrainvillamide in cell cultureJ. Am. Chem. Soc.129(16)4898-4899(2007) 3.Hu, L., Zhang, T., Liu, D., et al.Notoamide-type alkaloid induced apoptosis and autophagy via a P38/JNK signaling pathway in hepatocellular carcinoma cellsRSC Adv.9(34)19855-19868(2019)

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)

Vulpinic and gyrophoric acids are known as ultraviolet filters for natural lichen populations, they can effectively prevent cytotoxic, apoptotic and cytoskeleton alterative activities of 2.5 J/cm(2) UVB in a dose-dependent manner, suggest that vulpinic and gyrophoric acids can be promising cosmetic ingredients to photo-protect human skin cells. Gyrophoric acid also has anti-proliferative/cytotoxic effect.

Glycoside St-J (Compound 2), a triterpenoid saponin isolated from Anemone flaccida, exhibits antitumor activity by inhibiting HeLa cell proliferation and shows potential for use in the development of novel anticancer agents [1].

Methyl brevifolincarboxylate (Brevifolincarboxylic acid methyl ester) is a potent influenza virus PB2 cap-binding inhibitor. Methyl brevifolincarboxylate exhibits inhibitory activity against influenza virus A/Puerto Rico/8/34 (H1N1) and A/Aichi/2/68 (H3N2) with IC50s of 27.16 μM and 33.41 μM. Anti-oxidant activity[1][2]. Methyl brevifolincarboxylate exhibits significant DPPH radical scavenging activity with an IC50 value of 8.9 μM. [1]. Wu QY, et al. Chromatographic fingerprint and the simultaneous determination of five bioactive components of geranium carolinianum L. water extract by high performance liquid chromatography. Int J Mol Sci. 2011;12(12):8740-8749. [2]. Fang SH, et al. Anti-oxidant and inflammatory mediator's growth inhibitory effects of compounds isolated from Phyllanthus urinaria. J Ethnopharmacol. 2008;116(2):333-340.

α-D-Glucose-1,6-bisphosphate is abis-phosphorylated derivative of α-D-glucose that has roles in carbohydrate metabolism.1It is the product of the reaction of glucose-1- or 6-phosphate with glucose-1,6-bisphosphate synthase (PGM2LI) in the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate.2It is also a cofactor for the bacterial enzyme phosphopentomutase.3,4α-D-Glucose-1,6-bisphosphate has been used in the study of carbohydrate metabolism. 1.Beitner, R.Regulation of carbohydrate metabolism by glucose 1,6-bisphosphate in extrahepatic tissues; comparison with fructose 2,6-bisphosphateInt. J. Biochem.22(6)553-557(1990) 2.Maliekal, P., Sokolova, T., Vertommen, D., et al.Molecular identification of mammalian phosphopentomutase and glucose-1,6-bisphosphate synthase, two members of the α-D-phosphohexomutase familyJ. Biol. Chem.282(44)31844-31851(2007) 3.Moustafa, H.M.A., Zaghloul, T.I., and Zhang, Y.-H.P.A simple assay for determining activities of phosphopentomutase from a hyperthermophilic bacterium Thermotoga maritimaAnal. Biochem.50175-81(2016) 4.Panosian, T.D., Nannemann, D.P., Watkins, G.R., et al.Bacillus cereus phosphopentomutase is an alkaline phosphatase family member that exhibits an altered entry point into the catalytic cycleJ. Biol. Chem.286(10)8043-8054(2011)

Aspergillimide is a fungal metabolite originally isolated from A. japonicus.1 It reduces nicotinic acetylcholine receptor (nAChR) peak and slowly-desensitizing amplitudes induced by acetylcholine in silkworm (B. mori) larval neurons (IC50s = 20.2 and 39.6 nM, respectively) but has no effect on chicken α3β4-, α4β2-, and α7-containing nAChRs.2 Dietary administration of aspergillimide A (10 μg/g of diet) induces paralysis in silkworm fourth instar larvae.1 Aspergillimide A (10 and 20 mg/kg) reduces T. colubriformis fecal egg count in gerbils.3References1. Hayashi, H., Nishimoto, Y., Akiyama, K., et al. New paralytic alkaloids, asperparalines A, B and C, from Aspergillus japonicus JV-23. Biosci. Biotechnol. Biochem. 64(1), 111-115 (2000).2. Hirata, K., Kataoka, S., Furutani, S., et al. A fungal metabolite asperparaline a strongly and selectively blocks insect nicotinic acetylcholine receptors: The first report on the mode of action. PLoS One 6(4), e18354 (2011).3. Banks, R.M., Blanchflower, S.E., Everett, J.R., et al. Novel anthelmintic metabolites from an Aspergillus species; the aspergillimides. J. Antibiot. (Tokyo) 50(10), 840-846 (1997). Aspergillimide is a fungal metabolite originally isolated from A. japonicus.1 It reduces nicotinic acetylcholine receptor (nAChR) peak and slowly-desensitizing amplitudes induced by acetylcholine in silkworm (B. mori) larval neurons (IC50s = 20.2 and 39.6 nM, respectively) but has no effect on chicken α3β4-, α4β2-, and α7-containing nAChRs.2 Dietary administration of aspergillimide A (10 μg/g of diet) induces paralysis in silkworm fourth instar larvae.1 Aspergillimide A (10 and 20 mg/kg) reduces T. colubriformis fecal egg count in gerbils.3 References1. Hayashi, H., Nishimoto, Y., Akiyama, K., et al. New paralytic alkaloids, asperparalines A, B and C, from Aspergillus japonicus JV-23. Biosci. Biotechnol. Biochem. 64(1), 111-115 (2000).2. Hirata, K., Kataoka, S., Furutani, S., et al. A fungal metabolite asperparaline a strongly and selectively blocks insect nicotinic acetylcholine receptors: The first report on the mode of action. PLoS One 6(4), e18354 (2011).3. Banks, R.M., Blanchflower, S.E., Everett, J.R., et al. Novel anthelmintic metabolites from an Aspergillus species; the aspergillimides. J. Antibiot. (Tokyo) 50(10), 840-846 (1997).

Schiarisanrin A (Kadsulignan J), a lignan, exhibits inhibitory activity on nitric oxide (NO) production, demonstrating an IC50 of 9.6 μM in BV-2 cells [1].

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).

Cerebroside C is a fungal metabolite and glycosphingolipid that has been found in the rice pathogenic fungusM. grisea.1It induces production of the phytoalexin momilactone A when applied to wounded rice leaves, indicating that cerebroside C is an elicitor of the hypersensitive response in rice. Cerebroside C increases germination rate and reduces germination time in wheat seeds in a concentration-dependent manner at 4°C.2It also increases root length, fresh weight, and dry weight of wheat seedlings when used at a concentration of 20 μg/ml at 4°C, indicating increased chilling tolerance. 1.Koga, J., Yamuchi, T., Shimura, M., et al.Cerebrosides A and C, sphingolipid elicitors of hypersensitive cell death and phytoalexin accumulation in rice plantsJ. Biol. Chem.273(48)31985-31991(1998) 2.Li, H.-X., Xiao, Y., Cao, L.-L., et al.Cerebroside C increases tolerance to chilling injury and alters lipid composition in wheat rootsPLoS One8(9)e73380(2013)

Sporogen-AO 1 is a fungal metabolite originally isolated fromA. oryzaethat has diverse biological activities.1,2,3,4,5It inhibits HIV-1 Tat transactivation in a cell-based assay with an IC50value of 15.8 μM.4Sporogen-AO 1 is cytotoxic to HeLa, KB, and NCI H187 cancer cells (IC50s = 8.3, 9, and 5.1 μM, respectively).2,5It is active againstC. albicans(MIC = 4 mM).3 1.Tanaka, S., Wada, K., Marumo, S., et al.Structure of sporogen-ao 1, a sporogenic substance of Aspergillus oryzaeTetrahedron Lett.25(51)5907-5910(1984) 2.Motohashi, K., Hashimoto, J., Inaba, S., et al.New sesquiterpenes, JBIR-27 and -28, isolated from a tunicate-derived fungus, Penicillium sp. SS080624SCf1J. Antibiot. (Tokyo)62(5)247-250(2009) 3.Yurchenko, A., Smetanina, O.F., Kalinovsky, A., et al.Biologically active metabolites of the facultative marine fungus Penicillium citrinumChem. Nat. Compd.48(6)996-998(2013) 4.Jayasuriya, H., Zink, D.L., Polishook, J.D., et al.Identification of diverse microbial metabolites as potent inhibitors of HIV-1 Tat transactivationChem. Biodivers.2(1)112-122(2005) 5.Tansakul, C., Rukachaisirikul, V., Chalothorn, T., et al.Synthesis and cytotoxicity against KB and NCI-H187 cell lines of sporogen AO-1 analoguesPhytochem. Lett.22128-132(2017)

Piliformic acid is a fungal metabolite that has been found inN. pseudotrichiaand has diverse biological activities.1,2It is cytotoxic to BC-1 human breast cancer cells (IC50= 5 μg/ml).2Piloformic acid is active againstL. braziliensisamastigotes (IC50= 78.5 μM). It is also active against the plant pathogenic fungiC. gloeosporioides(MIC = 292 μM).1 1.Elias, L.M., Fortkamp, D., Sartori, S.B., et al.The potential of compounds isolated from Xylaria spp. as antifungal agents against anthracnoseBraz. J. Microbiol.49(4)840-847(2018) 2.Cota, B.B., Tunes, L.G., Maia, D.N.B., et al.Leishmanicidal compounds of Nectria pseudotrichia, an endophytic fungus isolated from the plant Caesalpinia echinata (Brazilwood)Mem. Inst. Oswaldo Cruz113(2)102-110(2018)

Aspulvinone O is a fungal metabolite that has been found in P. variotti and has antioxidant and anticancer activities.1,2 It scavenges 2,2-diphenyl-1-picrylhydrazyl radicals in a cell-free assay (IC50 = 11.6 μM).1 Aspulvinone O inhibits aspartate transaminase 1 (GOT1; Kd = 3.32 μM) and is cytotoxic to PANC-1, AsPC-1, and SW1990 pancreatic cancer cells (IC50s = 20.54-26.8 μM).2 It reduces the oxygen consumption rate (OCR) and induces apoptosis in SW1990 cells. Aspulvinone O (2.5 and 5 mg/kg) reduces tumor growth in an SW1990 mouse xenograft model. |1. Zhang, P., Li, X.-M., Wang, J.-N., et al. New butenolide derivatives from the marine-derived fungus Paecilomyces variotii with DPPH radical scavenging activity. Phytochem. Lett. 11, 85-88 (2015).|2. Sun, W., Luan, S., Qi, C., et al. Aspulvinone O, a natural inhibitor of GOT1 suppresses pancreatic ductal adenocarcinoma cells growth by interfering glutamine metabolism. Cell Commun. Signal. 17(1), 111 (2019).

Terpendole I is a fungal metabolite that has been found in A. yamanashiensis.1 It is a weak inhibitor of acyl-coenzyme A:cholesterol acyltransferase (ACAT; IC50 = 145 μM) and is active against the bacteria B. cereus and B. subtilis (MICs = 100 μg/ml for both) but not S. aureus, P. aeruginosa, or K. pneumoniae (MICs = >200 μg/ml for all) or the fungus C. albicans (MIC = 200 μg/ml).1,2 It is cytotoxic to HeLa cells with an IC50 value of 52.6 μM.3 |1. Tomoda, H., Tabata, N., Yang, D.-J., et al. Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. III. Production, isolation and structure elucidation of new components. J. Antibiot. (Tokyo) 48(8), 793-804 (1995).|2. Zhao, J.-C., Wang, Y.-L., Zhang, T.-Y., et al. Indole diterpenoids from the endophytic fungus Drechmeria sp. as natural antimicrobial agents. Phytochemistry 148, 21-28 (2018).|3. Nagumo, Y., Motoyama, T., Hayashi, T., et al. Structure-activity relationships of terpendole E and its natural derivatives. ChemistrySelect 2(4), 1533-1536 (2017).

Phenylpyropene A is a fungal metabolite originally isolated from P. griseofulvum that has enzyme inhibitory and insecticidal activities.1,2,3 It inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT; IC50 = 0.8 μM).1 Phenylpyropene A inhibits diacylglycerol acyltransferase (DGAT) in rat liver microsomes (IC50 = 78.7 μM). It induces mortality in 100% of M. persicae when used at a concentration of 5 ppm.3 |1. Kwon, O.E., Rho, M.C., Song, H.Y., et al. Phenylpyropene A and B, new inhibitors of acyl-CoA: Cholesterol acyltransferase produced by Penicillium griseofulvum F1959. J. Antibiot. (Tokyo) 55(11), 1004-1008 (2002).|2. Lee, S.W., Rho, M.C., Choi, J.H., et al. Inhibition of diacylglycerol acyltransferase by phenylpyropenes produced by Penicillium griseofulvum F1959. J. Microbiol. Biotechnol. 18(11), 1785-1788 (2008).|3. Horikoshi, R., Goto, K., Mitomi, M., et al. Identification of pyripyropene A as a promising insecticidal compound in a microbial metabolite screening. J. Antibiot. (Tokyo) 70(3), 272-276 (2017).

15-deoxy-Δ-12,14-Prostaglandin J2 is a PPARγ agonist.

Juglone (Regianin) is a natural naphthoquinone found in the black walnut (J. nigra) and other plants in the Juglandaceae family. Juglone also irreversibly inhibits peptidyl-prolyl cis/trans isomerases of the parvulin family, including human Pin1, yeast Ess1/Ptf1, and E. coli parvulin (Ki = 55.9 nM). Juglone also blocks transcription by RNA polymerases I, II, and III (IC50s = 2-7 μM) and attenuates kidney fibrosis in rats treated with unilateral ureteral obstruction, both through Pin1-independent mechanisms.

Bile acids are essential for solubilization and transport of dietary lipids, are the major products of cholesterol catabolism, and are physiological ligands for farnesoid X receptor (FXR), a nuclear receptor that regulates genes involved in lipid metabolism.1They are also inherently cytotoxic, as physiological imbalance contributes to increased oxidative stress.2,3Bile acid-controlled signaling pathways are promising novel targets to treat such metabolic diseases as obesity, type II diabetes, hyperlipidemia, and atherosclerosis.Guggulsterone, derived from resin of the guggul tree, is a competitive antagonist of FXR bothin vitroandin vivo.4Thecisstereoisomer of guggulsterone, (E)-guggulsterone, decreases chenodeoxycholic acid (CDCA)-induced FXR activation with an IC50value of 15 μM.5,6By inhibiting CDCA-induced transactivation of FXR, guggulsterone lowers low-density lipoprotein cholesterol and triglyceride levels in rodents fed a high cholesterol diet.4 1.Makishima, M., Okamoto, A.Y., Repa, J.J., et al.Identification of a nuclear receptor for bile acidsScience2841362-1365(1999) 2.Barbier, O., Torra, I.P., Sirvent, A., et al.FXR induces the UGT2B4 enzyme in hepatocytes: A potential mechanism of negative feedback control of FXR activityGastroenterology1241926-1940(2003) 3.Tan, K.P., Yang, M., and Ito, S.Activation of nuclear factor (erythroid-2 like) factor 2 by toxic bile acids provokes adaptive defense responses to enhance cell survival at the emergence of oxidative stressMol. Pharmacol.72(5)1380-1390(2007) 4.Urizar, N.L., Liverman, A.B., Dodds, D.T., et al.A natural product that lowers cholesterol as an anatagonist ligand for FXRScience296(5573)1703-1706(2002) 5.Cui, J., Huang, L., Zhao, A., et al.Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pumpThe Journal of Biological Chemisty278(12)10214-10220(2003) 6.Wu, J., Xia, C., Meier, J., et al.The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptorMolecular Endocrinology16(7)1590-1597(2002)

Oosporein is a mycotoxin that has been found inBeauveriaand has diverse biological activities.1,2It is cytotoxic to Sf9 and Sf21 insect cells with 50% cytotoxic concentration (CC50) values of 4.23 and 10.43 μM, respectively.3Oosporin induces lethality in day-old cockerels (LD50= 6.12 mg/kg).4It inhibits Na+/K+-, Ca2+-, and Mg2+-ATPase activities by 27, 52, and 100%, respectively, in equine erythrocyte ghosts when used at a concentration of 200 μg/ml.2Oosporein inhibits herpes simplex 1 (HSV-1), but not HeLa cell orE. coli, DNA polymerase (IC50s = 75, 610, and >700 μM, respectively).5It is active against the bacteriumS. pneumoniae(MIC = 32 μg/ml) and the plant pathogenic fungusP. infestans(MIC = 16 μM).1,6 1.Wainwright, M., Betts, R.P., and Teale, D.M.Antibiotic activity of oosporein from Verticillium psalliotaeTrans. Br. Mycol. Soc.86(1)168-170(1986) 2.Jeffs, L.B., and Khachatourians, G.G.Toxic properties of Beauveria pigments on erythrocyte membranesToxicon. 35(8)1351-1356(1997) 3.Arboleda Valencia, J.W., Gaitán Bustamante, A.L., Jiménez, A.V., et al.Cytotoxic activity of fungal metabolites from the pathogenic fungus Beauveria bassiana: An intraspecific evaluation of beauvericin productionCurr. Microbiol.63(3)306-312(2011) 4.Cole, R.J., Kirksey, J.W., Cutler, H.G., et al.Toxic effects of oosporein from Chaetomium trilateraleJ. Agric. Food Chem.22(3)517-520(1974) 5.Terry, B.J., Liu, W.C., Cianci, C.W., et al.Inhibition of herpes simplex virus type 1 DNA polymerase by the natural product oosporeinJ. Antibiot. (Tokyo)45(2)286-288(1992) 6.Nagaoka, T., Nakata, K., Kouno, K., et al.Antifungal activity of oosporein from an antagonistic fungus against Phytophthora infestansZ. Naturforsch. C. J. Biosci.59(3-4)302-304(2004)

Collinin is a coumarin that has been found in Z. schinifolium and has diverse biological activities.1,2,3,4 It is active against drug-susceptible and -resistant strains of M. tuberculosis (MIC50s = 3.13-6.25 μg/ml).1 Collinin inhibits LPS-induced nitric oxide (NO) production (IC50 = 5.9 μM) and reduces COX-2 protein levels in RAW 264.7 cells.2 It completely inhibits aggregation of isolated rabbit platelets induced by arachidonic acid , collagen, or platelet activating factor (PAF) when used at a concentration of 100 μM.3 Dietary administration of collinin (0.05% w/w) reduces the number of mice with tumors and the number of tumors per mouse in a mouse model of colitis-related carcinogenesis.4 |1. Kim, S., Seo, H., Al Mahmud, H., et al. In vitro activity of collinin isolated from the leaves of Zanthoxylum schinifolium against multidrug- and extensively drug-resistant Mycobacterium tuberculosis. Phytomedicine 46, 104-110 (2018).|2. Nguyen, P.-H., Zhao, B.T., Kim, O., et al. Anti-inflammatory terpenylated coumarins from the leaves of Zanthoxylum schinifolium with α-glucosidase inhibitory activity. J. Nat. Med. 70(2), 276-281 (2016).|3. I.S., C., Lin, Y.C., Tsai, I.L., et al. Coumarins and anti-platelet aggregation constituents from Zanthoxylum schinifolium. Phytochemistry 39(5), 1091-1097 (1995).|4. Kohno, H., Suzuki, R., Curini, M., et al. Dietary administration with prenyloxycoumarins, auraptene and collinin, inhibits colitis-related colon carcinogenesis in mice. Int. J. Cancer 118(12), 2936-2942 (2006).

Nardoguaianone J, a guaiane-type compound isolated from the roots of Nardostachys chinensis, has been shown to enhance SERT activity [1][2].

Echistatin TFA, the smallest active RGD protein belonging to the family of disintegrins that are derived from snake venoms, is a potent inhibitor of platelet aggregation. Echistatin is a potent inhibitor of bone resorption in culture. Echistatin is a potent antagonist of αIIbβ3, αvβ3 and α5β1[1][2][3][4]. [1]. J Musial, et al. Inhibition of platelet adhesion to surfaces of extracorporeal circuits by disintegrins. RGD-containing peptides from viper venoms. Circulation. 1990 Jul;82(1):261-73.[2]. M Sato, et al. Echistatin is a potent inhibitor of bone resorption in culture. J Cell Biol. 1990 Oct;111(4):1713-23.[3]. C C Kumar, et al. Biochemical characterization of the binding of echistatin to integrin alphavbeta3 receptor. J Pharmacol Exp Ther. 1997 Nov;283(2):843-53.[4]. I Wierzbicka-Patynowski, et al. Structural requirements of echistatin for the recognition of alpha(v)beta(3) and alpha(5)beta(1) integrins. J Biol Chem. 1999 Dec 31;274(53):37809-14.

Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013). Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3 References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013).

21-Deoxycortisol is a corticosteroid metabolite of 17-hydroxyprogesterone produced in the adrenal glandvia11-hydroxylation by 11β-hydroxylase.1,2Serum levels of 21-deoxycortisol are elevated in patients with congenital adrenal hyperplasia that are heterozygous for mutations inCYP2A21, the gene encoding steroid 21-hydroxylase, and have been used as a biomarker for the detection of 21-hydroxylase deficiencies. 1.Fiet, J., Villette, J.-M., Galons, H., et al.The application of a new highly-sensitive radioimmunoassay for plasma 21-deoxycortisol to the detection of steroid-21-hydroxylase deficiencyAnn. Clin. Biochem.31(Pt. 1)56-64(1994) 2.Cristoni, S., Cuccato, D., Sciannamblo, M., et al.Analysis of 21-deoxycortisol, a marker of congenital adrenal hyperplasia, in blood by atmospheric pressure chemical ionization and electrospray ionization using multiple reaction monitoringRapid Commun. Mass Spectrom.18(1)77-82(2004)

Stachybotrysin B is a fungal metabolite originally isolated from S. chartarum and has antiviral and anticancer activities.1,2 It has antiviral activity against HIV in SupT1 cells (IC50 = 19.2 μM).1 Stachybotrysin B is cytotoxic to K562, HeLa, and HL-60 cells (IC50s = 21.72, 39.63, and 18.5 μM, respectively).2 |1. Zhao, J., Feng, J., Tan, Z., et al. Stachybotrysins A-G, phenylspirodrimane derivatives from the fungus Stachybotrys chartarum. J. Nat. Prod. 80(6), 1819-1826 (2017).|2. Ma, X.-h., Zheng, W.-m., Sun, K.-h., et al. Two new phenylspirodrimanes from the deep-sea derived fungus Stachybotrys sp. MCCC 3A00409. Nat. Prod. Res. 33(3), 386-392 (2018).

Gliovirin is a fungal metabolite that has been found inT. harzianumand has fungicidal, antimicrobial and anti-inflammatory activities.1It is active against the plant pathogenic fungusP. ultimum(MIC = 60 ng/ml) and the parasiteT. brucei brucei(IC50= 90 ng/ml), but has no effect on the plant pathogenic fungiR. solani,P. omnivorum,T. basicola,R. arrhizus, andV. dahliaeor the bacteriaB. thuringiensis,P. fluorescens, andX. malvacearumwhen used at concentrations up to 1,000 ng/ml.2,3Gliovirin decreases phorbol 12-myristate 13-acetate (TPA)- and ionomycin-induced increased expression of COX-2 (IC50= 1 μM) and protein levels of IL-2 in Jurkat cells (IC50= 5.2 μM).1 1.Rether, J., Serwe, A., Anke, T., et al.Inhibition of inducible tumor necrosis factor-α expression by the fungal epipolythiodiketopiperazine gliovirinBiol. Chem.388(6)627-637(2007) 2.Howell, C.R., and Stipanovic, R.D.Gliovirin, a new antibiotic from Gliocladium virens, and its role in the biological control of Pythium ultimumCan. J. Microbiol.29(3)321-324(1983) 3.Iwatsuki, M., Otoguro, K., Ishiyama, A., et al.In vitro antitrypanosomal activity of 12 low-molecular-weight antibiotics and observations of structure/activity relationshipsJ. Antibiot. (Tokyo)63(10)619-622(2010)