Frenolicins C-G, pyranonaphthoquinones from Streptomyces sp. RM-4-15.
Appalachian active coal fire sites were selected for the isolation of bacterial strains belonging to the class actinobacteria. A comparison of high-resolution electrospray ionization mass spectrometry (HRESIMS) and ultraviolet (UV) absorption profiles from isolate extracts to natural product databases suggested Streptomyces sp. RM-4-15 to produce unique metabolites. Four new pyranonaphthoquinones, frenolicins C-F (1-4), along with three known analogues, frenolicin (6), frenolicin B (7), and UCF76-A (8), were isolated from the fermentation of this strain. An additional new analogue, frenolicin G (5), along with two known compounds, deoxyfrenolicin (9) and UCF 13 (10), were isolated from the fermentation supplied with 18 mg/L of scandium chloride, the first example, to the best of our knowledge, wherein scandium chloride supplementation led to the confirmed production of new bacterial secondary metabolites. Structures 1-5 were elucidated on the basis of spectral analysis and chemical modification. While frenolicins are best known for their anticoccidial activity, the current study revealed compounds 6-9 to exhibit moderate cytotoxicity against the human lung carcinoma cell line (A549) and thereby extends the anticancer SAR for this privileged scaffold.
Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, Kentucky 40536-0596, USA.
Xiachang
X
Wang
Khaled A
KA
Shaaban
Sherif I
SI
Elshahawi
Larissa V
LV
Ponomareva
Manjula
M
Sunkara
Yinan
Y
Zhang
Gregory C
GC
Copley
James C
JC
Hower
Andrew J
AJ
Morris
Madan K
MK
Kharel
Jon S
JS
Thorson
D039903:Actinobacteria / Q000737:chemistry*; D001061:Appalachian Region; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013302:Streptomyces / Q000737:chemistry; D013329:Structure-Activity Relationship; D000095622:Benzoisochromanequinones
D009285:Naphthoquinones; D011753:Pyrones; C424927:UCF76-A; C584588:frenolicin C; C018066:frenolicin B; D000095622:Benzoisochromanequinones; C004673:deoxyfrenolicin