title: Potential chemopreventive activity of a new macrolide antibiotic from a marine-derived Micromonospora sp.
abstract: Agents capable of inducing phase II enzymes such as quinone reductase 1 (QR1) are known to have the potential of mediating cancer chemopreventive activity. As part of a program to discover novel phase II enzyme-inducing molecules, we identified a marine-derived actinomycete strain (CNJ-878) that exhibited activity with cultured Hepa 1c1c7 cells. Based on this activity, a new macrolide, juvenimicin C (1), as well as 5-O-α-L-rhamnosyltylactone (2), were isolated from the culture broth of a Micromonospora sp. Compound 1 enhanced QR1 enzyme activity and glutathione levels by two-fold with CD values of 10.1 and 27.7 μM, respectively. In addition, glutathione reductase and glutathione peroxidase activities were elevated. This is the first reported member of the macrolide class of antibiotics found to mediate these responses.
authors.affiliation: Department of Medical Chemistry & Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA. scarls21@uic.edu
authors.forename: Skylar
authors.initials: S
authors.lastname: Carlson
authors.forename: Laura
authors.initials: L
authors.lastname: Marler
authors.forename: Sang-Jip
authors.initials: SJ
authors.lastname: Nam
authors.forename: Bernard D
authors.initials: BD
authors.lastname: Santarsiero
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
authors.forename: Brian T
authors.initials: BT
authors.lastname: Murphy
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D018942:Macrolides / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008847:Micromonospora / Q000378:metabolism*
chemical_list: C585608:5-O-alpha-L-rhamnosyltylactone; D000900:Anti-Bacterial Agents; D016588:Anticarcinogenic Agents; D018942:Macrolides; C585607:juvenimicin C; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase
references.citation: Planta Med. 2003 Jan;69(1):15-20
references.pmid: 12567273
references.citation: Cancer Res. 1997 Jan 15;57(2):272-8
references.pmid: 9000567
references.citation: Toxicology. 2006 Oct 29;227(3):217-26
references.pmid: 16971035
references.citation: Toxicol Lett. 1995 Dec;82-83:173-9
references.pmid: 8597048
references.citation: Org Biomol Chem. 2008 Sep 21;6(18):3315-27
references.pmid: 18802638
references.citation: Appl Environ Microbiol. 2004 Dec;70(12):7520-9
references.pmid: 15574955
references.citation: J Agric Food Chem. 2011 Mar 23;59(6):2332-40
references.pmid: 21332190
references.citation: Bioorg Med Chem. 2011 Nov 1;19(21):6182-95
references.pmid: 21978950
references.citation: Int J Syst Evol Microbiol. 2012 Feb;62(Pt 2):272-278
references.pmid: 21398502
references.citation: Int J Syst Evol Microbiol. 2012 Mar;62(Pt 3):716-721
references.pmid: 22140171
references.citation: Anal Biochem. 1988 Mar;169(2):328-36
references.pmid: 3382006
references.citation: Anticancer Res. 2010 Dec;30(12):4873-82
references.pmid: 21187465
references.citation: Free Radic Biol Med. 2000 Aug;29(3-4):231-40
references.pmid: 11035251
references.citation: Cancer Res. 1999 Feb 1;59(3):578-85
references.pmid: 9973203
references.citation: Arch Pharm Res. 2004 Sep;27(9):919-22
references.pmid: 15473661
references.citation: Fitoterapia. 2012 Dec;83(8):1506-13
references.pmid: 22960348
references.citation: Bioorg Med Chem. 2012 Dec 15;20(24):7030-9
references.pmid: 23142320
references.citation: J Agric Food Chem. 2002 Dec 4;50(25):7472-6
references.pmid: 12452678
references.citation: Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2399-403
references.pmid: 1549603
references.citation: J Nat Prod. 2003 Sep;66(9):1197-202
references.pmid: 14510596