Quantitation of the specific interaction of [14a-3H] cryptopleurine with 80S and 40S ribosomal species from the yeast Saccharomyces cerevisiae

Doelz, H.; Vázquez, David; Jiménez, Antonio Moreno

doi:10.1021/bi00256a023

Cited by 34 publications

(14 citation statements)

References 31 publications

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“…However, the specific biomolecular targets of these compounds on cell growth have not been clearly identified until now. Early studies illustrated that phenanthroindolizidine alkaloids could inhibit RNA, DNA synthesis, and inhibited protein synthesis at the elongation stage of the translation procedure by locating on 40S ribosomal component [15]–[20]. Recently, some possible targets were reported, including metabolic enzymes [21]–[23] and some elements engaged in gene transcription [24], [25].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Biological Evaluation and Mechanism Studies of Deoxytylophorinine and Its Derivatives as Potential Anticancer Agents

Ren

et al. 2012

PLoS ONE

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Previous studies indicated that (+)-13a-(S)-Deoxytylophorinine (1) showed profound anti-cancer activities both in vitro and in vivo and could penetrate the blood brain barrier to distribute well in brain tissues. CNS toxicity, one of the main factors to hinder the development of phenanthroindolizidines, was not obviously found in 1. Based on its fascinating activities, thirty-four derivatives were designed, synthesized; their cytotoxic activities in vitro were tested to discover more excellent anticancer agents. Considering the distinctive mechanism of 1 and interesting SAR of deoxytylophorinine and its derivatives, the specific impacts of these compounds on cellular progress as cell signaling transduction pathways and cell cycle were proceeded with seven representative compounds. 1 as well as three most potent compounds, 9, 32, 33, and three less active compounds, 12, 16, 35, were selected to proform this study to have a relatively deep view of cancer cell growth-inhibitory characteristics. It was found that the expressions of phospho-Akt, Akt, phospho-ERK, and ERK in A549 cells were greater down-regulated by the potent compounds than by the less active compounds in the Western blot analysis. To the best of our knowledge, this is the first report describing phenanthroindolizidines alkaloids display influence on the crucial cell signaling proteins, ERK. Moreover, the expressions of cyclin A, cyclin D1 and CDK2 proteins depressed more dramatically when the cells were treated with 1, 9, 32, and 33. Then, these four excellent compounds were subjected to flow cytometric analysis, and an increase in S-phase was observed in A549 cells. Since the molecular level assay results of Western blot for phospho-Akt, Akt, phospho-ERK, ERK, and cyclins were relevant to the potency of compounds in cellular level, we speculated that this series of compounds exhibit anticancer activities through blocking PI3K and MAPK signaling transduction pathways and interfering with the cell cycle progression.

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Section: Introductionmentioning

confidence: 99%

Synthesis, Biological Evaluation and Mechanism Studies of Deoxytylophorinine and Its Derivatives as Potential Anticancer Agents

Ren

et al. 2012

PLoS ONE

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“…2 Other studies suggested that these molecules might act via several mechanisms, possibly different from those of currently launched drugs. 3 Many potential targets have been reported, including inhibition of protein synthesis and ribosomal subunits, 4 inhibition of HIF-1, 5 thymidylate synthase and dihydrofolate reductase, 6 suppression of signaling pathways such as NF-κB, AP-1, and CRE, as well as a number of cell cycle regulatory proteins such as cyclin and cyclin dependent kinases. 3 …”

Section: Introductionmentioning

confidence: 99%

Antitumor Agents 295. E-Ring Hydroxylated Antofine and Cryptopleurine Analogues as Antiproliferative Agents: Design, Synthesis, and Mechanistic Studies

Yang¹,

Shi²,

Lai³

et al. 2012

J. Med. Chem.

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Various E-ring hydroxylated antofine and cryptopleurine analogs were designed, synthesized, and tested against five human cancer cell lines. Interesting structure-activity relationship (SAR) correlations were found among these new compounds. The most potent compound 13b was further tested against a series of non-small cell lung cancer (NSCLC) cell lines, in which it showed impressive antiproliferative activity. Mechanistic studies revealed that 13b is able to down-regulate HSP90 and β-catenin in A549 lung adenocarcinoma cells in a dose-dependent manner, suggesting a potential use for treating Hedgehog pathway-driven tumorigenesis.

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“…Due to their striking bioactivity, [3][4][5] the ipecac alkaloid emetine (1) and its synthetic derivative dehydroemetine have been used for the treatment of protozoal infections, such as amebiasis, trypanosomiasis and bilharziasis, which pose a constant threat to inhabitants of tropical areas. [6,7] In addition, emetine (1) has recently become an attractive anticancer and antiviral target.…”

mentioning

confidence: 99%

Synthesis of Bioactive 2‐Aza‐Analogues of Ipecac and Alangium Alkaloids

et al. 2010

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Quantitation of the specific interaction of [14a-3H] cryptopleurine with 80S and 40S ribosomal species from the yeast Saccharomyces cerevisiae

Cited by 34 publications

References 31 publications

Synthesis, Biological Evaluation and Mechanism Studies of Deoxytylophorinine and Its Derivatives as Potential Anticancer Agents

Synthesis, Biological Evaluation and Mechanism Studies of Deoxytylophorinine and Its Derivatives as Potential Anticancer Agents

Antitumor Agents 295. E-Ring Hydroxylated Antofine and Cryptopleurine Analogues as Antiproliferative Agents: Design, Synthesis, and Mechanistic Studies

Synthesis of Bioactive 2‐Aza‐Analogues of Ipecac and Alangium Alkaloids

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