Isolation and identification of chlorinated genistein from Actinoplanes sp. HBDN08 with antioxidant and antitumor activities.
A strain Actinoplanes sp. HBDN08 was screened by PCR-guided method using primers derived from conserved regions of halogenase genes. A new chlorinated isoflavone, 3',8-dichlorogenistein (1), along with 8-chlorogenistein (2) were isolated from the fermentation broth of Actinoplanes sp. HBDN08. Their structures were elucidated on the basis of extensive 1D and 2D NMR as well as HRESI-MS, ESI-MS, UV, and IR spectroscopic analyses. The origin of the two compounds was also investigated by high-performance liquid chromatography (HPLC) analysis. The results demonstrated that they were not biosynthesized but derived from the biotransformation of genistein by Actinoplanes sp. HBDN08. The antioxidant activities of the isolated compounds 1 and 2 were evaluated by using the lipid peroxidation assay. Their antitumor activities were calculated according to the inhibitory rate of cell proliferation against the human breast cancer cell line MDA-MB-231. The results indicated that compounds 1 (IC(50) = 5.2 microM) and 2 (IC(50) = 7.5 microM) showed stronger antioxidant activities than genistein (IC(50) = 13.6 microM). In comparison with the antitumor activities of genistein, those of compounds 1 and 2 increased 7.7- and 2.6-fold, respectively. These results suggest that the PCR-guided screening strategy is a rapid method for obtaining halometabolite-producing strains. Moreover, these results reveal that chlorination has significant effects on the bioactivities of genistein. This could be important information for studying the structure-activity relationships of genistein.
Xiang
Wen-Sheng
WS
School of Life Science, Northeast Agricultural University, Harbin 150030, PR China.
Zhang
Ji
J
Wang
Ji-Dong
JD
Jiang
Ling
L
Jiang
Bing
B
Xiang
Zhi-Dan
ZD
Wang
Xiang-Jing
XJ
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005285:Fermentation; D019833:Genistein / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008848:Micromonosporaceae / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D000975:Antioxidants; D019833:Genistein