Structure−Activity Relationship Analysis of Novel Derivatives of Narciclasine (an <i>Amaryllidaceae</i> Isocarbostyril Derivative) as Potential Anticancer Agents

Ingrassia, Laurent; Lefranc, Florence; Dewelle, Janique; Pottier, Laurent; Mathieu, Véronique; Spiegl-Kreinecker, Sabine; Sauvage, Sébastien; Yazidi, Mohamed El; Dehoux, Mischaël; Berger, Walter; Quaquebeke, Eric Van; Kiss, Róbert

doi:10.1021/jm8013585

Cited by 142 publications

(213 citation statements)

References 47 publications

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“…The overall growth level of human U373, A549 and PC-3 cancer cells was determined by means of the MTT colorimetric assay as detailed elsewhere (15,17,18). The cancer cells were cultured for 3 days in the presence (or absence as a control) of ISP concentrations ranging from 1 nM to 10 μM.…”

Section: Isp In Vitro Growth Inhibitory Activitymentioning

confidence: 99%

“…Apoptosis and necrosis were determined using flow cytometry analyses of Annexin V/propidium iodide double staining, as detailed elsewhere (15,18,19,23). Experiments were performed in triplicate.…”

Section: In Vitro Computer-assisted Phase-contrast Microscopy Analysementioning

confidence: 99%

“…ISP induces cytotoxic effects in human U373 GBM cells. The human U373 GBM cells resist many types of pro-apoptotic stimuli even when the pro-apoptotic compounds are analyzed at concentrations up to 10-fold the compound-related IC 50 concentrations (17,18,23). Fig.…”

Section: Determination Of Isp Ic 50 In Vitro Growth Inhibitory Concenmentioning

confidence: 99%

“…We used as a positive control the human PC-3 prostate cancer cell line in which plantderived compounds, such as narciclasine (15) or sodium pump inhibitors (16) are able to induce apoptosis in vitro. Narciclasine and sodium pump inhibitors are not able to induce apoptosis in vitro in the U373 GBM (17,18) and A549 NSCLC (19) models: these two models therefore display a certain level of resistance to apoptosis. (15,17,18).…”

Section: Introductionmentioning

confidence: 99%

“…Narciclasine and sodium pump inhibitors are not able to induce apoptosis in vitro in the U373 GBM (17,18) and A549 NSCLC (19) models: these two models therefore display a certain level of resistance to apoptosis. (15,17,18). ISP was obtained as described elsewhere (9); its chemical structure is illustrated in Fig.…”

Section: Introductionmentioning

confidence: 99%

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Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, with potential anti-tumor activity against apoptosis-resistant cancer cells

Baldé

Mégalizzi²,

Cao³

et al. 2010

Int J Oncol

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Abstract. Isostrychnopentamine (ISP) is an indolomonoterpenic alkaloid that is present in the leaves of Strychnos usambarensis, an East African small tree. We have reported previously pro-apoptotic effects induced in vitro by ISP in the human HCT-116 colon cancer cell line, a model that displays relative sensitivity to apoptosis. In the present study, we observed that the in vitro growth inhibitory activities of ISP are similar in cancer cells that display sensitivity versus resistance to apoptosis. We made use of the U373 glioblastoma and the A549 non-small cell lung cancer (NSCLC) cell lines as models relatively resistant to apoptosis, and the human PC-3 prostate cancer cell line as a model relatively sensitive to apoptosis. While ISP induced transient decreases in [ATP] i and apoptosis in human U373 GBM cells, it did not provoke such features in A549 NSCLC cells. It thus seems that ISPinduced anti-cancer activity can lead to pro-apoptotic effects as a consequence, while apoptosis seems not to be the main cause by which ISP induces cancer cell death. ISP is a compound that merits further investigations in order to: i) identify the mechanism(s) of action by which it kills cancer cells, and ii) hemisynthesize novel ISP derivatives aiming to overcome, at least partly, the resistance of metastatic cancers to apoptosis. IntroductionDespite frequent responses to chemotherapy, curative treatment remains elusive for the majority of patients with metastatic solid tumors (1). Indeed, in the common advanced cancers, over 40 years of cytotoxic drug development has brought no significant change in cure rates (1). Savage and colleagues (1) report that one interpretation is that the intrinsic properties of the malignancies themselves, rather than the qualities of individual drugs or combination therapies, are primarily responsible for their curability with chemotherapy. These authors thus suggest that the curability of these malignancies results from an intrinsic 'locked-in' state of sensitivity to proapoptotic stresses in these cells (1). In fact, >90% of cancer patients die from their metastases (2). Drug resistance, either acquired or intrinsic, often prevents tumor cells from undergoing sufficient levels of apoptosis, resulting in cancer cell survival and treatment failure (1,2). The metastatic process is inherent to a significant level of resistance to apoptosis. Indeed, as a barrier to metastases, cells normally undergo apoptosis after they lose contact with their extra cellular matrix or their neighboring cells (3). This cell death process has been termed 'anoikis' (3). Tumor cells that acquire malignant potential have developed mechanisms to resist anoikis and thereby survive after detachment from their primary site and while travelling through the lymphatic and circulatory systems (3). Defects in the death receptor pathway of caspase activation, such as the over-expression of the caspase-8 inhibitor FLIP, can render cells resistant to anoïkis (3).Plants have played a dominant role in the development of sophisticate...

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Section: Isp In Vitro Growth Inhibitory Activitymentioning

confidence: 99%

Section: In Vitro Computer-assisted Phase-contrast Microscopy Analysementioning

confidence: 99%

Section: Determination Of Isp Ic 50 In Vitro Growth Inhibitory Concenmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, with potential anti-tumor activity against apoptosis-resistant cancer cells

Baldé

Mégalizzi²,

Cao³

et al. 2010

Int J Oncol

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Synthesis of (+)‐trans‐Dihydrolycoricidine by an Organocatalytic Enantioselective Friedel–Crafts Reaction

et al. 2016

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The amaryllidaceae alkaloid (+ +)-trans-dihydrolycoricidine (1)w as synthesized by asymmetric organocatalytic Friedel-Craftsr eaction of sesamol with nitro-olefin followed by an intramolecular Henry reaction for constructiono ft he Cr ing system.C onstructiono ft he Br ing was achieved by am icrowave-assisted palladium-catalyzed CO insertion reaction. Finally,r egio-and stereoselective introductiono ft he third hydroxyl group (at C3) on the Cr ing afforded 1.

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Milde Rhodium(III)‐katalysierte C‐H‐Aktivierung und intermolekulare Anellierung mit Allenen

Wang¹,

Glorius²

2012

Angewandte Chemie

112

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Alle(ne) großartig! Eine neue RhIII‐katalysierte oxidative Kupplung mit Allenen unter milden Bedingungen liefert Heterocyclen mit exocyclischen Doppelbindungen. Diese Reaktion benötigt nur geringe Katalysatormengen und bietet eine hohe Regio‐ und Stereoselektivität sowie eine exzellente Substratbreite. Es wurden eine Derivatisierung der Produkte sowie erste mechanistische Studien durchgeführt.

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Structure−Activity Relationship Analysis of Novel Derivatives of Narciclasine (an Amaryllidaceae Isocarbostyril Derivative) as Potential Anticancer Agents

Cited by 142 publications

References 47 publications

Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, with potential anti-tumor activity against apoptosis-resistant cancer cells

Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, with potential anti-tumor activity against apoptosis-resistant cancer cells

Synthesis of (+)‐trans‐Dihydrolycoricidine by an Organocatalytic Enantioselective Friedel–Crafts Reaction

Milde Rhodium(III)‐katalysierte C‐H‐Aktivierung und intermolekulare Anellierung mit Allenen

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