Cytotoxic benzo[j]fluoranthene metabolites from Hypoxylon truncatum IFB-18, an endophyte of Artemisia annua.
Two new benzo[j]fluoranthene-based secondary metabolites named daldinone C (1) and daldinone D (2), along with two known metabolites, altechromone A and (4S)-5,8-dihydroxy-4-methoxy-alpha-tetralone, were isolated from the CHCl3/MeOH (1:1) extract of a solid culture of the endophyte Hypoxylon truncatum IFB-18 harbored inside the symptomless stem tissue of Artemisia annua. The structures of the new compounds were elucidated by MS and 1D and 2D NMR spectra and by X-ray diffraction analysis. Their absolute configurations were determined unambiguously by a combination of their CD data and the established exciton chirality rule. Compounds 1 and 2 were substantially cytotoxic against SW1116 cells, with IC50 values of 49.5 and 41.0 microM, respectively, comparable to that (37.0 microM) of 5-fluorouracil. The biosynthetic pathway for 1 and 2 was postulated with the natural occurrence of benzo[j]fluoranthene analogues discussed in brief.
Gu
W
W
Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, School of Medicine, Nanjing University, Nanjing 210093, People's Republic of China.
Ge
H M
HM
Song
Y C
YC
Ding
H
H
Zhu
H L
HL
Zhao
X A
XA
Tan
R X
RX
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D031172:Artemisia annua; D001203:Ascomycota / Q000737:chemistry*; D002681:China; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D005449:Fluorenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D015394:Molecular Structure; D010946:Plants, Medicinal
D000970:Antineoplastic Agents; D005449:Fluorenes; C517717:daldinone C; C517716:daldinone D; C027704:benzo(j)fluoranthene