A highly potent antiangiogenic activity of retinoids

Oikawa, Tsutomu; Hirotani, Kenji; Nakamura, Osamu; Shudo, Koichi; Hiragun, Akiyoshi; Iwaguchi, Takao

doi:10.1016/0304-3835(89)90054-2

Cited by 130 publications

(59 citation statements)

References 25 publications

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“…Several types of angiogenesis inhibitors such as angiostatic steroids, 18) retinoid 19) and cartilage factors 20) have been discovered, although they are not clinically useful due to toxicity and potency. Therefore, it is of interest to search for new types of angiogenesis inhibitors.…”

Section: Resultsmentioning

confidence: 99%

5-Demethoxyfumagillol, a Potent Angiogenesis Inhibitor Isolated from Aspergillus fumigatus

Kim

Min

Ahn

et al. 2004

CHEMICAL & PHARMACEUTICAL BULLETIN

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Angiogenesis, the phenomenon of generating a new capillary vessels, has a close connection with various diseases 1) such as the growth and transfer of solid cancer, rheumatoid arthritis, diabetic retinopathy, and psoriasis. In 1971, Judah Folkman of the Medical College of Harvard University, U.S.A., suggested the novel concept of treating solid tumors by inhibiting angiogenesis.2) Recent clinical studies on antiangiogenic agents seem to indicate that the problem of tolerance associated with conventional anti-cancer agents could be alleviated, probably by acting directly on the endothelial cells rather than on tumor cells of a living organism.Fifty years ago, Hanson and Eble reported that cultures of a fungus Aspergillus fumigatus (IMI-069714) inhibited Staphylococcus aureus 209 bacteriophage.3) The structure and stereochemistry of the active constituent fumagillin was determined by X-ray crystallographic studies.4) Also, in 1990, Ingber et al. 5) reported that fumagillin (2) showed potent anti-angiogenic activity and inhibited endothelial cell proliferation in vitro and tumor-induced angiogenesis in vivo.6,7) However, the effectiveness of 2 as an inhibitor of tumor growth was limited because it produced severe weight loss as a side effect. Ingber et al. started chemical modification of 2 in an effort to obtain analogues having the potent anti-angiogenic activity of 2 with less toxicity. As a result, one of the semi-synthetic derivatives, TNP-470 (4), has been found to have more potent anti-angiogenic activity and be less toxic compared to 2.8-10) TNP-470 (4) is currently one of the most promising small molecule inhibitors of angiogenesis and is being evaluated in phase III clinical trials as a potential anti-cancer drug. [11][12][13][14] In the course of our search for a new type of anti-angiogenesis inhibitors from cultured broths of soil microorganisms, 5-demethoxyfumagillol (1), a novel anti-angiogenic substance, was obtained by basic hydrolysis of 5-demethoxyfumagillin. 15) In the present paper, we describe the fermentation, isolation, and saponification of 5-demethoxyfumagillin, and structural assignment of 1 by spectroscopic analysis and independent synthesis (Chart 2). In addition, the preparation of a 5-demethoxyfumagillol analogue with a carbamoyl side chain and its anti-angiogenic activity are reported.Chemistry To confirm the structure of 5-demethoxyfumagillol (1), semi-synthetic 1 was synthesized from fumagillol (3) as a starting material. First, oxidation of 3 by the Collins reagent, 16) followed by reductive elimination of the resulting 6-ketofumagillol (5) by treatment with samarium(II) diiodide (SmI 2 ), 17) produced the desired demethoxylated 6-ketofumagillol 6 in 50% yield. Then, stereoselective reduction of ketone 6 with L-selectride (lithium tri-sec-butylborohydride, 1.0 M solution in tetrahydrofuran) furnished 83% yield of the desired 1, along with 13% of epimeric 6-epi-5-demethoxyfumagillol (1). Finally, in order to examine the anti-angiogenic activities of demethoxyfumagillol derivative...

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Section: Resultsmentioning

confidence: 99%

5-Demethoxyfumagillol, a Potent Angiogenesis Inhibitor Isolated from Aspergillus fumigatus

Kim

Min

Ahn

et al. 2004

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…The CAM assay was performed as previously described (12,13). In brief, fertilized chicken eggs were kept in a humidified incubator at 37°C.…”

Section: Cam Angiogenesis Assaymentioning

confidence: 99%

“…In CAM assay, anti-angiogenic activities of either 15K or YM155 were judged on 7th day after 2 days treatment, and retinoic acid (RA, 5 nmol/egg) was used as a positive (anti-angiogenic) control (13,15). As shown in Figure 2, 15K significantly inhibited the new blood vessel growth of chick embryos in a dose-dependent manner (0.2-20 nmol/egg).…”

Section: Suppression Of Embryonic Angiogenesis In Ovo By 15k and Ym155mentioning

confidence: 99%

Both triazolyl ester of ketorolac (15K) and YM155 inhibit the embryonic angiogenesis <i>in ovo</i> (fertilized eggs) <i>via</i> their common PAK1-survivin/VEGF signaling pathway

Ahn

Bae

Jeong

et al. 2017

DD&T

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“…This compound is known to reversibly inhibit the phosphorylation of VEGFR tyrosine kinase. Additionally, 2 0 ,4 0 -dihydroxy-6 0 -methoxy-3 0 ,5 0 -dimethylchalcone abrogates VEGFR-mediated signal transduction via suppression of MAPK and Akt activation [78,126,135,152,174,193]. Because hydroxylated chalcones are frequent in nature, 2 0 -hydroxy-4 0 -methoxychalcone (32) was investigated [99].…”

Section: Inhibition Of Angiogenesismentioning

confidence: 99%

“…These compounds include boronic acid chalcone [78], chalcone analogues related to curcumin [174], various chalcone derivatives with a substituted backbone [126,152], and chalcone carboxylic acid [135].…”

Section: Inhibition Of Angiogenesismentioning

confidence: 99%

Dietary chalcones with chemopreventive and chemotherapeutic potential

et al. 2011

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Chalcones are absorbed in the daily diet and appear to be promising cancer chemopreventive agents. Chalcones represent an important group of the polyphenolic family, which includes a large number of naturally occurring molecules. This family possesses an interesting spectrum of biological activities, including antioxidative, antibacterial, anti-inflammatory, anticancer, cytotoxic, and immunosuppressive potential. Compounds of this family have been shown to interfere with each step of carcinogenesis, including initiation, promotion and progression. Moreover, numerous compounds from the family of dietary chalcones appear to show activity against cancer cells, suggesting that these molecules or their derivatives may be considered as potential anticancer drugs. This review will focus primarily on prominent members of the chalcone family with an 1,3-diphenyl-2-propenon core structure. Specifically, the inhibitory effects of these compounds on the different steps of carcinogenesis that reveal interesting chemopreventive and chemotherapeutic potential will be discussed.

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A highly potent antiangiogenic activity of retinoids

Cited by 130 publications

References 25 publications

5-Demethoxyfumagillol, a Potent Angiogenesis Inhibitor Isolated from Aspergillus fumigatus

5-Demethoxyfumagillol, a Potent Angiogenesis Inhibitor Isolated from Aspergillus fumigatus

Both triazolyl ester of ketorolac (15K) and YM155 inhibit the embryonic angiogenesis <i>in ovo</i> (fertilized eggs) <i>via</i> their common PAK1-survivin/VEGF signaling pathway

Dietary chalcones with chemopreventive and chemotherapeutic potential

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