Isolation and structure elucidation of a novel androgen antagonist, arabilin, produced by Streptomyces sp. MK756-CF1

Kawamura, Tatsuro; Fujimaki, Takahiro; Hamanaka, Natsuki; Torii, Kentaro; Kobayashi, Hiroki; Takahashi, Yoshikazu; Igarashi, Masayuki; Kinoshita, Naoko; Nishimura, Yoshio; Tashiro, Etsu; Imoto, Masaya

doi:10.1038/ja.2010.98

Cited by 22 publications

(27 citation statements)

References 14 publications

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“…Compounds 1 , 2 , and 10 were proved to be known compounds of flavofungins I ( 1 ) and II ( 2 ) 30, 31 and spectinabilin ( 10 ) 32–34 based on their HRESIMS and NMR data (Tables 1 and 2) as well as a comparison to the data of references. Flavofungins I ( 1 ) and II ( 2 ) were 32-membered polyene-polyol macrolides with a conjugated chain of five unsubstituted double bonds connected to a polyol fragment with eight hydroxy groups alternated.…”

Section: Resultsmentioning

confidence: 99%

“…Flavofungins I ( 1 ) and II ( 2 ) were 32-membered polyene-polyol macrolides with a conjugated chain of five unsubstituted double bonds connected to a polyol fragment with eight hydroxy groups alternated. Both flavofungins I ( 1 ) and II ( 2 ) were reported to have antifungal and antiviral activities 19 , while spectinabilin ( 10 ) was a nitro-substituted polyketide with activity to block the binding of androgen to the ligand-binding domain of androgen receptor 34 .…”

Section: Resultsmentioning

confidence: 99%

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Rare Polyene-polyol Macrolides from Mangrove-derived Streptomyces sp. ZQ4BG

Wang

Song

Chai

et al. 2017

Sci Rep

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Bioactive natural products from mangrove-derived actinomycetes are important sources for discovery of drug lead compounds. In this study, an extract prepared from culture of an actinomycete Streptomyces sp. ZQ4BG isolated from mangrove soils was found to have activity in inhibiting proliferation of glioma cells. Large culture of this mangrove actinomycete in Gause’s liquid medium resulted in isolation of seven novel polyene-polyol macrolides, named as flavofungins III–IX (3–9), together with known flavofungins I (1) and II (2) and spectinabilin (10). Structures of these isolated compounds were elucidated by extensive NMR analyses and HRESIMS data. The stereochemical assignments were achieved by a combination of NOE information, universal NMR database, and chemical reactions including preparation of acetonide derivatives and Mosher esters. Flavofungins IV–VIII (4–8) are rare 32-membered polyene-polyol macrolides with a tetrahydrofuran ring, while flavofungin IX (9) represents the first example of this type of macrolide with a unique oxepane ring. Flavofungins I (1) and II (2) and spectinabilin (10) showed anti-glioma and antifungal activities.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Rare Polyene-polyol Macrolides from Mangrove-derived Streptomyces sp. ZQ4BG

Wang

Song

Chai

et al. 2017

Sci Rep

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“…A B * * * * overexpression and being hypersensitive to low levels of androgens in vitro. Subsequent screening of other thiohydantoin derivatives revealed that CH5137291 exhibited antitumor activity in CRPC xenografts where CH4933468 failed to prevent their growth [78].…”

Section: Thiohydantoin Derivativesmentioning

confidence: 99%

Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist Activity

Miyata¹

2015

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE May 2015 REPORT TYPEFinal Annual Summary PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERJohn s Hopkins Uni versity 600 N. Wolfe Street Baltimore, Maryland 21287 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTWe hypothesized that dehydroepiandrosterone metabolites or their synthetic derivatives are able to bind to the androgen receptor with low, if any, agonist activity and thus function as better antiandrogens than currently available ones. We preliminarily identified three potential dehydroepiandrosterone derivatives with marginal androgenic activity. In this project, we assessed the effects of these compounds, in comparison with classic antiandrogens clinically used, on cell proliferation/apoptosis, cell migration/invasion, and prostate-specific antigen expression in prostate cancer lines in vitro as well as on tumor growth in animal models for prostate cancer and found their inhibitory effects on androgen-mediated tumor outgrowth. We further dissected molecular mechanisms of how such compounds suppress the progression of prostate cancer and found that they could alter androgen-mediated androgen receptor functions in prostate cancer cells. Importantly, these dehydroepiandrosterone derivatives were found to possess marginal agonist effects on the activity of androgen receptor. SUBJECT TERMS IntroductionAlthough antiandrogens that can block androgen action through the androgen receptor (AR) have been widely used for the treatment of prostate cancer, the majority of available agents possess agonist activity, resulting in increases in serum prostate-specific antigen (PSA) levels, known as the antiandrogen withdrawal syndrome [1,2]. In addition, we previously demonstrated that androstenediol, a physiological metabolite from dehydroepiandrosterone (DHEA) and a precursor of testosterone, has an ...

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“…MK756-CF1, the new polypropionate derivative, arabilin Fig. (2), was proved to be a competitive ligand of AR, showing an inhibitory activity on the androgen-induced prostate-specific antigen mRNA expression in prostate cancer LNCaP cells [86].…”

Section: Natural Androgen Receptor (Ar) Ligandsmentioning

confidence: 99%

Natural Ligands for Nuclear Receptors: Biology and Potential Therapeutic Applications

D’Auria¹,

Sepe²,

Zampella

2012

CTMC

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Nuclear receptors are key regulators of various processes including reproduction, development, and metabolism of xeno- and endobiotics. Research in the last two decades has focused to the development of novel drugs specifically targeting nuclear receptors for the treatment of a variety of diseases, such as cancer, diabetes, dyslipidemia, fatty liver disease, drug hepatotoxicity and cholestasis. The search for novel NRs agonists and antagonists with enhanced selectivity prompted the exploration of the extraordinary chemical diversity associated to natural products. In recent years a number of natural products were disclosed as ligands of NRs and proved to have remarkable affinity and in some cases peculiar mode of action. In this review the natural ligands of the subfamily NR1, NR2, and NR3 will be described with an emphasis to their mechanisms of action and pharmacological profiles.

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Isolation and structure elucidation of a novel androgen antagonist, arabilin, produced by Streptomyces sp. MK756-CF1

Cited by 22 publications

References 14 publications

Rare Polyene-polyol Macrolides from Mangrove-derived Streptomyces sp. ZQ4BG

Rare Polyene-polyol Macrolides from Mangrove-derived Streptomyces sp. ZQ4BG

Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist Activity

Natural Ligands for Nuclear Receptors: Biology and Potential Therapeutic Applications

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