Antioxidant and cytotoxic activities of canadine: Biological effects and structural aspects

Correche, Estela; Andújar, Sebastián Antonio; Kurdelas, Rita R.; Lechón, María José Gómez; Freile, M.L.; Enriz, Ricardo D.

doi:10.1016/j.bmc.2008.02.015

Cited by 40 publications

(19 citation statements)

References 28 publications

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“…Anonaine has also exhibited dose‐dependent antiproliferative, antimigratory and DNA‐damaging effects on H1299 cells and can be useful for chemoprevention of human lung cancer . Our results corroborate the cytotoxic action of anonaine as previously reported for HepG2 (CC 50 values of 33.5 μg/ml), while for HeLa and hepatocytes, the CC 50 values were 24.8 and 70.3 μg/ml, respectively, indicating that anonaine possesses cytotoxic activity in different cell lines.…”

Section: Resultssupporting

confidence: 90%

Antiplasmodial activity and cytotoxicity, isolation of active alkaloids, and dereplication of Xylopia sericea leaves ethanol extract by UPLC-DAD-ESI-MS/MS

Gontijo

Brandão

Nascimento

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives To assess the antiplasmodial activity of the ethanol extract of Xylopia sericea leaves, Annonaceae, often associated with antimalarial use and to perform a bioguided isolation of active compounds. Methods Dereplication of ethanol extract by the UPLC‐DAD‐ESI‐MS/MS technique allowed the identification of the major constituents, isolation and identification of alkaloids. The antiplasmodial and cytotoxic activity of the extract, fractions and isolated compounds was evaluated against the chloroquine‐resistant W2 strain Plasmodium falciparum and HepG2 cells, respectively. Key findings Ethanol extract showed high reduction of parasitemia as well as moderate cytotoxicity (86.5 ± 3.0% growth inhibition at 50 μg/ml and CC50 72.1 ± 5.1 μg/ml, respectively). A total of eight flavonoids were identified, and two aporphine alkaloids, anonaine and O‐methylmoschatoline, were isolated. Anonaine disclosed significant antiplasmodial effect and moderate cytotoxicity (IC50 23.2 ± 2.7 μg/ml, CC50 38.3 ± 2.3 μg/ml, SI 1.6) while O‐methylmoschatoline was not active against P. falciparum and showed a low cytotoxicity (33.5 ± 1.9% growth inhibition at 50 μg/ml, CC50 274.4 ± 0.5 μg/ml). Conclusions Characterization of Xylopia sericea leaves ethanol extract by UPLC‐DAD‐ESI‐MS/MS as well as its antiplasmodial activity and the occurrence of anonaine and O‐methylmoschatoline in this Xylopia species are reported by the first time.

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Section: Resultssupporting

confidence: 90%

Antiplasmodial activity and cytotoxicity, isolation of active alkaloids, and dereplication of Xylopia sericea leaves ethanol extract by UPLC-DAD-ESI-MS/MS

Gontijo

Brandão

Nascimento

et al. 2019

Journal of Pharmacy and Pharmacology

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“…Canadine is one of the analogues, which closely resembles the structure of berberine [ 42 ]. However the saturated double bonds in the isoquinoline ring might alter its aromaticity [ 42 ], thereby interrupting it’s binding with the G-quadruplex (Fig. 5a ).…”

Section: Resultsmentioning

confidence: 99%

“…To further confirm the specificity of berberine in targeting the G-quadruplex structure, we took advantage of the structure-activity relationship that mediates the binding with this structure. Canadine resembles the structure of berberine but it has a tertiary amine group due to the saturation of the double bonds in the isoquinoline ring, which alters its planarity due to the loss of π electrons [ 42 ]. This disrupts the binding potential of canadine with the G-quadruplex thereby exhibiting no biological activity in the TT cells.…”

Section: Discussionmentioning

confidence: 99%

Selective repression of RET proto-oncogene in medullary thyroid carcinoma by a natural alkaloid berberine

et al. 2015

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BackgroundThe gain-of-function mutation of the RET proto-oncogene, which encodes a receptor tyrosine kinase, is strongly associated with the development of several medullary thyroid carcinomas (MTCs). Thus, the RET protein has been explored as an excellent target for progressive and advanced MTC. In this study we have demonstrated a therapeutic strategy for MTC by suppressing the transcription of RET proto-oncogene though the stabilization of G-quadruplex structure formed on the promoter region of this gene using a natural product berberine.MethodsMedullary thyroid carcinoma (MTC) TT cell line has been used to evaluate the effects of berberine on RET expression and its downstream signaling pathways. The specificity of berberine was demonstrated by using the papillary thyroid carcinoma TPC1 cell line, which lacks the G-quadruplex forming sequence on the RET promoter region due to chromosomal rearrangement.ResultsBerberine suppressed the RET expression by more than 90 % in MTC TT cells at a concentration of 2.5 μg/ml with minimal effect on the TPC1 cells. Canadine, which is a structural analogue of berberine, showed little interaction with RET G-quadruplex and also had no effect on RET expression in MTC TT cells. The down-regulation of RET with berberine further inhibited the cell proliferation through cell cycle arrest and activation of apoptosis in TT cells, which was confirmed by a 2-fold increase in the caspase-3 activity and the down-regulation of cell-cycle regulatory proteins.ConclusionOur data strongly suggest that the G-quadruplex forming region and the stabilization of this structure play a critical role in mediating the repressive effect of berberine on RET transcription.

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“…To confirm the results obtained from the acute toxicity study, we performed a study of cytotoxicity of three representative compounds of this series (compounds 2a , 2b , and 13 ) using the well‐known MTT bioassay. We have previously used this technique successfully to the study of other compounds of biological interest .…”

Section: Resultsmentioning

confidence: 99%

A New Series of Antibacterial Nitrosopyrimidines: Synthesis and Structure–Activity Relationship

Olivella

Marchal

Nogueras

et al. 2014

Archiv der Pharmazie

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New nitrosopyrimidines were synthesized and evaluated as potential antibacterial agents. Different compounds structurally related with 4,6-bis(alkyl or arylamino)-5-nitrosopyrimidines were evaluated. Some of these nitrosopyrimidines displayed significant antibacterial activity against human pathogenic bacteria. Among them compounds 1c, 2a-c, and 9a-c exhibited remarkable activity against methicillin-sensitive and -resistant Staphylococcus aureus, Escherichia coli, Yersinia enterocolitica, and Salmonella enteritidis. A detailed structure-activity relationship study, supported by theoretical calculations, aided us to identify and understand the minimal structural requirements for the antibacterial action of the nitrosopyrimidines reported here. Thus, our results have led us to identify a topographical template that provides a guide for the design of new nitrosopyrimidines with antibacterial effects.

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Antioxidant and cytotoxic activities of canadine: Biological effects and structural aspects

Cited by 40 publications

References 28 publications

Antiplasmodial activity and cytotoxicity, isolation of active alkaloids, and dereplication of Xylopia sericea leaves ethanol extract by UPLC-DAD-ESI-MS/MS

Antiplasmodial activity and cytotoxicity, isolation of active alkaloids, and dereplication of Xylopia sericea leaves ethanol extract by UPLC-DAD-ESI-MS/MS

Selective repression of RET proto-oncogene in medullary thyroid carcinoma by a natural alkaloid berberine

A New Series of Antibacterial Nitrosopyrimidines: Synthesis and Structure–Activity Relationship

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