p 12

3β-Hydroxy-27-p-Z-coumaroyloxyurs-12-en-28-oic acid (compound 8) is a triterpene ester HIV-1 protease inhibitor with potential for use in antiretroviral combination therapy for AIDS.

Lauric Acid (Dodecylic acid),which is found naturally in various plant and animal fats and oils, is a saturated medium-chain fatty acid with a 12-carbon backbone. It is a major component of coconut oil and palm kernel oil.

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)

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).

Sphingosine (d14:1) is a bioactive sphingolipid that has been found in B. mori (silkworm), P. clarkii (crayfish), and A. aurita (jellyfish) extracts. It increases the germination rate of N. rileyi, an entomopathogenic fungus, with an EC50 value of 10.2 nM. Sphingosine (d14:1) inhibits protein kinase C (PKC) in vitro (IC50 = 7.3 mol%) as well as superoxide generation induced by phorbol 12-myristate 13-acetate in neutrophils and reduces growth of CHO cells (IC50s = 19 and 8 μM, respectively).

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).

1. Homogentisic acid (2,5-dihydroxyphenylacetic acid) shows interesting antioxidant and antiradical activities, and protective effect against thermal-cholesterol degradation, comparable to those of well known antioxidants. 2. Homogentisic acid is the primary precursor of melanin synthesis in Vibrio cholerae, a Hyphomonas strain, and Shewanella colwelliana. 3. A derivative of homogentisic acid which inhibits Pfnek-1 with an IC(5) around 1.8 muM, this product is moderately active in vitro against a FcB1 P. falciparum strain (IC(5) = 12 muM).

3-O-(E)-p-coumaroyl tormentic acid may be promising lead compound for developing an effective drug for treatment of leukemia, it induces apoptotic cell death in human leukemia (HL60) via mainly mitochondrial pathway by, at least in part, Topo I inhibition. 3-O-trans-p-coumaroyltormentic acid shows cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) in vitro, the IC50 values of 13.72, 14.29,14.61, 14.04 uM, respectively. 3beta-O-cis-p-Coumaroyltormentic acid, and 3beta-O-trans-p-coumaroyltormentic acid are weakly selective for vancomycin-resistant Enterococcus (VRE) compared with eukaryotic cells, with an MIC of 59.4microg mL and a 50% inhibitory concentration (IC50) of 72.0microg mL for monkey kidney epithelial (MA104) cells. A mixture of 3-O-cis-p-coumaroyltormentic acid and 3-O-trans-p-coumaroyltormentic acid shows an inhibitory effect comparable to (-)-epigallocatechin gallate (EGCG) of green tea on the activation of Epstein-Barr virus early antigen (EBV-EA) induced by 12-O-tetradeca--noylphorbol-13-acetate (TPA).

Glycozolidal (compound 12) is a carbazole alkaloid that exhibits antimicrobial activity against Porphyromonas gingivalis (P. gingivalis). In vitro studies have shown that Glycozolidal displays cytotoxic effects on human gingival fibroblasts (HGFs) and monocytic cells (U937), with IC50 values of 120.86 µg mL and 97.74 µg mL, respectively.