Identification of a Novel Cardenolide (2‘ ‘-Oxovoruscharin) from Calotropis procera and the Hemisynthesis of Novel Derivatives Displaying Potent in Vitro Antitumor Activities and High in Vivo Tolerance:  Structure−Activity Relationship Analyses

Quaquebeke, Eric Van; Simon, Gentiane; Andre, Aurélie; Dewelle, Janique; Yazidi, Mohamed El; Bruyneel, Frédéric; Tuti, Jérôme; Nacoulma, Odile; Guissou, Pierre I.; Decaestecker, Christine; Braekman, Jean Claude; Kiss, Róbert; Darro, Francis

doi:10.1021/jm049405a

Cited by 153 publications

(136 citation statements)

References 49 publications

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“…normal levels of apoptosis in cancer cells and also potentially block tumorigenesis and inflammation (33,34). Yet digitoxinmediated inhibition of the NF-B signaling pathway in cystic fibrosis lung epithelial cells has been demonstrated to be mechanistically distinct from Na ϩ ͞K ϩ -ATPase inhibition (23).…”

Section: Resultsmentioning

confidence: 99%

Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization

Langenhan¹,

Peters²,

Guzei³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

218

174

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Glycosylated natural products are reliable platforms for the development of many front-line drugs, yet our understanding of the relationship between attached sugars and biological activity is limited by the availability of convenient glycosylation methods. When a universal chemical glycosylation method that employs reducing sugars and requires no protection or activation is used, the glycorandomization of digitoxin leads to analogs that display significantly enhanced potency and tumor specificity and suggests a divergent mechanistic relationship between cardiac glycosideinduced cytotoxicity and Na ؉ ͞K ؉ -ATPase inhibition. This report highlights the remarkable advantages of glycorandomization as a powerful tool in glycobiology and drug discovery.carbohydrate ͉ natural product ͉ sugar

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Section: Resultsmentioning

confidence: 99%

Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization

Langenhan¹,

Peters²,

Guzei³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

218

174

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“…The compound displayed anti-tumour activity against a panel of 57 human cancer cell lines that is comparable to taxol, and stronger than SN-38, two of the most potent drugs used in hospitals to treat cancer [55]. Against Hs683, U373, HCT-15, LoVo and A549, the IC 50 values of UNBS1450 (3, 9, 24, 10 and 8 nM) were superior to those of 2"-oxovoruscharin (8,15,16,10 and 74 nM), respectively.…”

Section: Calotropis Proceramentioning

confidence: 97%

“…Chemical modification of 2´´-oxovoruscharin, a novel cardenolide isolated from the root bark of C. procera, has led to the synthesis of UNBS1450, a compound characterized by more potent antiproliferative activity and lower toxicity [55,64,65]. The compound displayed anti-tumour activity against a panel of 57 human cancer cell lines that is comparable to taxol, and stronger than SN-38, two of the most potent drugs used in hospitals to treat cancer [55].…”

Section: Calotropis Proceramentioning

confidence: 99%

“…This non-apoptotic cancer cell death mediated by nucleolar targeting and down-regulation of c-Myc expression is a new mechanism of anti-tumour action. Through disorganization of the actin cytoskeleton, the compound possesses both anti-proliferative and antimigratory properties [55,64,65]. UNBS1450 has shown to be a potent sodium pump inhibitor and induces non-apoptotic cell death.…”

Section: Calotropis Proceramentioning

confidence: 99%

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Cytotoxic Cardenolides from Calotropis Species: A Short Review

Chan¹,

Sweidan²,

Wong³

et al. 2017

Rec.Nat.Prod.

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Abstract:From different plant parts of Calotropis species (C. gigantea and C. procera), various classes of compounds such as oxypregnanes, terpenoids, sterols, cardenolides and flavonoids have been isolated. Of these compounds, the cardenolides stand out as many of them have anticancer properties. Cardenolides are C 23 steroids with a five-membered unsaturated butyrolactone ring consisting of a steroid nucleus, a lactone moiety at C-17 and a sugar moiety at C-3. The roles of cardenolides in the treatment of human cancer have been established as they can induce apoptosis and inhibit the growth of cancer cells. Structure-activity relationship analyses have yielded some interesting findings on their cytotoxicity. Compounds with six-membered ring sugar groups generally have significantly stronger inhibitory activity than those with five-membered ring sugar groups. A formyl or methyl-hydroxyl group at C-10 enhances cytotoxicity while the presence of a 4´-OH or 16-OH group decreases cytotoxicity. Chemical modification of 2"-oxovoruscharin, a novel cardenolide extracted from the root bark of C. procera, has led to the synthesis of UNBS1450. The compound is characterized by more potent antiproliferative activity, lower toxicity, and is a strong sodium pump inhibitor and inducer of non-apoptotic cell death. UNBS1450 is currently in Phase I clinical trials.

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“…The overall growth level of human and mouse cancer cell lines and human normal cell lines was determined using the colorimetric MTT (3-[4,5-dimethylthiazol-2yL-diphenyl tetrazolium bromide, Sigma, Belgium) assay (23)(24)(25). Briefly, the cell lines were incubated for 24 h in 96-microwell plates (at a concentration of 10,000-40,000 cells/ml culture medium depending on the cell type) to ensure adequate plating prior to cell growth determination.…”

Section: Determining Ic 50 In Vitro Growth Inhibitory Concentrationsmentioning

confidence: 99%

Fourier Transform Infrared (FTIR) spectroscopy to monitor the cellular impact of newly synthesized platinum derivatives

Berger

Gasper²,

Lamoral-Theys³

et al. 2010

Int J Oncol

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Abstract. Platinum complexes remain widely used to combat various types of cancers. Three platinum complexes, cisplatin, carboplatin and oxaliplatin, are marketed for various oncological purposes. Additionally, nedaplatin, lobaplatin and heptaplatin have gained regionally limited approval for oncology purposes. Furthermore, various platinum derivatives are currently under clinical trials. More than 40 years after their discovery, however, the precise mechanism of action of platinum antitumor complexes remains elusive, partly because these compounds display numerous intracellular targets. Structure-activity-relationship analyses are therefore difficult to conduct to optimize the synthesis of novel platinum derivatives. The aim of the present study is to illustrate the potential of using Fourier Transform Infrared (FTIR) analyses to monitor the cellular modifications induced by the new platinum derivatives that we have synthesized. We show in the present study the advantages of combining an in vitro assay to determine the IC 50 growth inhibition concentrations of a series of compounds belonging to a given chemical series and FTIR analyses carried out at the IC 50 concentrations for each compound to identify potential hits within this series of compounds. The original pharmacological approach proposed here could, therefore, avoid large-scale pharmacological experiments to find hits within a given chemical series.

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Identification of a Novel Cardenolide (2‘ ‘-Oxovoruscharin) from Calotropis procera and the Hemisynthesis of Novel Derivatives Displaying Potent in Vitro Antitumor Activities and High in Vivo Tolerance: Structure−Activity Relationship Analyses

Cited by 153 publications

References 49 publications

Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization

Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization

Cytotoxic Cardenolides from Calotropis Species: A Short Review

Fourier Transform Infrared (FTIR) spectroscopy to monitor the cellular impact of newly synthesized platinum derivatives

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