Antitrypanosomal and antileishmanial activities of novel N-alkyl-(1-phenylsubstituted-β-carboline)-3-carboxamides

Tonin, Lilian Tatiani Düsman; Panice, Manuela Ribeiro; Nakamura, Celso Vataru; Rocha, Karin Juliane Pelizzaro; Santos, Adriana O.; Costa, Willian Ferreira da; Sarragiotto, María Helena

doi:10.1016/j.biopha.2010.02.006

Cited by 36 publications

(27 citation statements)

References 18 publications

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“…Scheme 1 shows a compilation of some of our works highlighting compounds with activity against different in vitro assays. [11][12][13][14][15][16][17] In a recent study from our group, 16 we showed that a series of 1-substituted phenyl 3-(2-oxo-1,3,4-oxadiazol-5-yl) and 3-(2-oxo-3-alkylaminomethyl-1,3,4-oxadiazolyl)-β-carboline derivatives presented in vitro antiproliferative activity against cancer cell lines, being more active for resistant ovarian (NCI-ADR/RES) and breast (MCF7) cancer cell lines. Investigation of the DNA interaction mode for the most active compound, 1-(4-N,Ndimethylaminophenyl)-3-(2-oxo-1,3,4-oxadiazol-5-yl) β-carboline, showed a strong interaction with DNA via intercalation, indicating that its action mechanism may be associated with this process.…”

Section: Introductionmentioning

confidence: 99%

Interaction of β-Carbolines with DNA: Spectroscopic Studies, Correlation with Biological Activity and Molecular Docking

Silva

Savariz

Silva-Júnior

et al. 2016

Journal of the Brazilian Chemical Society

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Quantitative interaction of twelve β-carboline derivatives with calf thymus deoxyribonucleic acid (ctDNA) using spectroscopic techniques was evaluated. The values of the binding constants (K b ) obtained for the complexes formed with the ctDNA ranged from 3.30 × 10 2 to 1.82 × 10 6 mol L −1 , being the β-carbolines with the N,N-dimethylaminophenyl group at position 1 the ones which presented the highest K b values. The binding mode between the β-carbolines evaluated and ctDNA was proposed from the KI assay, competition with ethidium bromide, and DNA thermal denaturation profile (T m ), where it was possible to infer that the evaluated alkaloids interact with ctDNA preferably via intercalation. Additionally, the correlation of K b values obtained with the IC 50 of seven human cancer cell lines was carried out. From this study, it was possible to observe a linear relation among most of the evaluated derivatives, obtaining r 2 values from 0.5360 to 0.9600. In addition, in silico molecular docking was performed to corroborate the experimental results.

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Section: Introductionmentioning

confidence: 99%

Interaction of β-Carbolines with DNA: Spectroscopic Studies, Correlation with Biological Activity and Molecular Docking

Silva

Savariz

Silva-Júnior

et al. 2016

Journal of the Brazilian Chemical Society

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“…␤-CB was synthesized as previously described by Tonin et al (8) and dissolved in DMSO before use. The molecular structure of the compound is shown in Fig.…”

Section: Methodsmentioning

confidence: 99%

“…␤-Carboline alkaloids have drawn attention because of their biological activities against parasites of the Trypanosomatidae family, including antitrypanosomal activity (6)(7)(8)(9)(10) and antileishmanial activity (8,(11)(12)(13). A recent study demonstrated the antileishmanial and antitrypanosomal activity of a series of N-alkyl-(1-phenyl-substituted-tetrahydro-␤-carboline)-3-carboxamides, showing that compounds containing Nbutylcarboxamide groups were the most active, suggesting that these groups may improve the biological activity of these compounds (8). In the present study, we assessed the antileishmanial activity of the ␤-carboline compound N-butyl- [1-(4-methoxy)-phenyl-9H-␤-carboline]-3-carboxamide (␤-CB) against different forms of L. amazonensis.…”

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confidence: 99%

N -Butyl-[1-(4-Methoxy)Phenyl-9 H -β-Carboline]-3-Carboxamide Prevents Cytokinesis in Leishmania amazonensis

Stefanello

Panice

Ueda-Nakamura

et al. 2014

Antimicrob Agents Chemother

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dLeishmaniasis, a complex of diseases caused by protozoa of the genus Leishmania, is endemic in 98 countries, affecting approximately 12 million people worldwide. Current treatments for leishmaniasis have many disadvantages, such as toxicity, high costs, and prolonged treatment, making the development of new treatment alternatives highly relevant. Several studies have verified the antileishmanial activity of ␤-carboline compounds. In the present study, we investigated the in vitro antileishmanial activity of N-butyl-[1-(4-methoxy)phenyl-9H-␤-carboline]-3-carboxamide (␤-CB) against Leishmania amazonensis. The compound was active against promastigote, axenic amastigote, and intracellular amastigote forms of L. amazonensis, exhibiting high selectivity for the parasite. Moreover, ␤-CB did not exhibit hemolytic or mutagenic potential. Promastigotes treated with the alkaloid presented rounding of the body cell, cell membrane projections, an increase in the number of promastigotes presenting two flagella, and parasites of abnormal phenotype, with three or more flagella and/or nuclei. Furthermore, we observed an increase in the subpopulation of cells in the G 2 /M stage of the cell cycle. Altogether, these results suggest that ␤-CB likely prevents cytokinesis, although it does not interfere with the duplication of cell structures. We also verified an increase in O 2 ·؊ production and the accumulation of lipid storage bodies. Cell membrane integrity was maintained, in addition to the absence of phosphatidylserine externalization, DNA fragmentation, and autophagosomes. Although the possibility of an apoptotic process cannot be discarded, ␤-CB likely exerts its antileishmanial activity through a cytostatic effect, thus preventing cellular proliferation.

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“…[7][8][9][10][11][12][13][14] Our research group demonstrated that β-carboline derivatives with various substituents at positions-1, 3 and 9 of the β-carboline skeleton presented significant in vitro antitumoral, antiviral, antitrypanosomal and antileishmanial activities. [15][16][17][18][19][20][21][22][23] Other studies have shown that β-carboline derivatives with a methyl-substituted group at position-1 and a guanidinium group-terminated side chain at C-3 exhibited anti-HIV-1 activity in MT4 cells by hindering the essential interaction of the regulatory protein Tat with trans-activation response region (TAR). 24,25 Some results cited above indicated that β-carboline derivatives containing 4-hydroxyphenyl, 4-methoxyphenyl or 3-nitrophenyl group at C-1 showed potent anticancer activity for some of the human cancer cell lines tested.…”

Section: Introductionmentioning

confidence: 99%

Synthesis,in vitroAntiproliferative and Anti-Mycobacterium tuberculosisActivities of Novel β-Carboline Derivatives

Moreira

Croda

Sarragiotto

et al. 2016

Journal of the Brazilian Chemical Society

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A series of β-carboline derivatives with amino or guanidinium were synthesized and evaluated in vitro against anti-Mycobacterium tuberculosis and for antiproliferative activities against nine human cancer cell lines. The compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) β-carboline (24.9 μg mL ) effectively inhibited growth and was highly selective against NCI/ADR. The in silico study revealed that 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) β-carboline, 1-(4-methoxyphenyl)-3-carboxamide(ethylamine) β-carboline, 1-(4-hydroxyphenyl)-3-carboxamide(propylamine) β-carboline, 1-(4-methoxyphenyl)-3-carboxamide(propylamine) β-carboline and 1-(3-nitrophenyl)-3-carboxamide(propylamine) β-carboline compounds follow the rules established by Lipinski, suggesting that this compound has no problems with oral bioavailability.

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Antitrypanosomal and antileishmanial activities of novel N-alkyl-(1-phenylsubstituted-β-carboline)-3-carboxamides

Cited by 36 publications

References 18 publications

Interaction of β-Carbolines with DNA: Spectroscopic Studies, Correlation with Biological Activity and Molecular Docking

Interaction of β-Carbolines with DNA: Spectroscopic Studies, Correlation with Biological Activity and Molecular Docking

N -Butyl-[1-(4-Methoxy)Phenyl-9 H -β-Carboline]-3-Carboxamide Prevents Cytokinesis in Leishmania amazonensis

Synthesis,in vitroAntiproliferative and Anti-Mycobacterium tuberculosisActivities of Novel β-Carboline Derivatives

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