Synthesis and anti-Trypanosoma cruzi activity of derivatives from nor-lapachones and lapachones

Júnior, Eufrânio N. da Silva; Souza, Maria Cecília B. V. de; Fernandes, Michelle Casal; Menna-Barreto, Rubem F.S.; Pinto, Maria do Carmo F. R.; Junior, Francisco de Assis da Silva Lopes; Simone, C. A. De; Andrade, Carlos Kleber Z.; Pinto, Antônio V.; Ferreira, Vı́tor F.; Castro, Solange L. de

doi:10.1016/j.bmc.2008.03.032

Cited by 71 publications

(34 citation statements)

References 26 publications

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“…Since the synthesis of arylamino substituted lapachones and azidoquinones are well established in our group [25,40,42], compounds 13 and 14 were prepared as shown in Scheme 3. Following click methodology, compounds 13 and 14 were reacted with selenium-containing azide and alkyne, respectively, to furnish the naphthoquinones 15 and 16 in 70% and 80% yield, respectively.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights

Cruz

Silvers

Jardim

et al. 2016

European Journal of Medicinal Chemistry

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Selenium-containing quinone-based 1,2,3-triazoles were synthesized using click chemistry, the copper catalyzed azide-alkyne 1,3-dipolar cycloaddition, and evaluated against six types of cancer cell lines: HL-60 (human promyelocytic leukemia cells), HCT-116 (human colon carcinoma cells), PC3 (human prostate cells), SF295 (human glioblastoma cells), MDA-MB-435 (melanoma cells) and OVCAR-8 (human ovarian carcinoma cells). Some compounds showed IC50 values < 0.3 μM. The cytotoxic potential of the quinones evaluated was also assayed using non-tumor cells, exemplified by peripheral blood mononuclear (PBMC), V79 and L929 cells. Mechanistic role for NAD(P)H:Quinone Oxidoreductase 1 (NQO1) was also elucidated. These compounds could provide promising new lead derivatives for more potent anticancer drug development and delivery, and represent one of the most active classes of lapachones reported.

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Section: Resultsmentioning

confidence: 99%

Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights

Cruz

Silvers

Jardim

et al. 2016

European Journal of Medicinal Chemistry

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“…Naphthoquinones have been found to be cytotoxic towards various human cancers including ovarian, breast, lung and cervical cancers lines (Bonifazi et al, 2010;da Silva Júnior et al, 2010), with many compounds displaying IC 50 values of -5 mM. This group of compounds has also been shown to exhibit trypanocidal activity (Ferreira et al, 2006;Silva et al, 2006;da Silva Júnior et al, 2008) and antiplasmodial activity. A group of aminonaphthoquinones was tested in P. falciparum (clones W2 and D6) growth inhibition assays, with one of the aminoquinones displaying higher potency than chloroquine towards the W2 clone (Kapadia et al, 2001).…”

Section: Discussionmentioning

confidence: 96%

Screening for small molecule modulators of Hsp70 chaperone activity using protein aggregation suppression assays: inhibition of the plasmodial chaperone PfHsp70-1

Cockburn

Pesce

Pryzborski

et al. 2011

Biological Chemistry

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Plasmodium falciparum heat shock protein 70 (PfHsp70-1) is thought to play an essential role in parasite survival and virulence in the human host, making it a potential antimalarial drug target. A malate dehydrogenase based aggregation suppression assay was adapted for the screening of small molecule modulators of Hsp70. A number of small molecules of natural (marine prenylated alkaloids and terrestrial plant naphthoquinones) and related synthetic origin were screened for their effects on the protein aggregation suppression activity of purified recombinant PfHsp70-1. Five compounds (malonganenone A-C, lapachol and bromo-β-lapachona) were found to inhibit the chaperone activity of PfHsp70-1 in a concentration dependent manner, with lapachol preferentially inhibiting PfHsp70-1 compared to another control Hsp70. Using growth inhibition assays on P. falciparum infected erythrocytes, all of the compounds, except for malonganenone B, were found to inhibit parasite growth with IC(50) values in the low micromolar range. Overall, this study has identified two novel classes of small molecule inhibitors of PfHsp70-1, one representing a new class of antiplasmodial compounds (malonganenones). In addition to demonstrating the validity of PfHsp70-1 as a possible drug target, the compounds reported in this study will be potentially useful as molecular probes for fundamental studies on Hsp70 chaperone function.

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“…There are numerous reports on synthetic approaches to generate BODIPY scaffold with bespoke spectral properties. 28 Among them, we used the methodology from the Dehaen group with minor modifications 30 for preparing compound 3. With regards to the azides 4-7,…”

Section: Resultsmentioning

confidence: 99%

On the synthesis of quinone-based BODIPY hybrids: New insights on antitumor activity and mechanism of action in cancer cells

Gontijo

Freitas

Emery

et al. 2017

Bioorganic & Medicinal Chemistry Letters

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Fluorescent quinone-based BODIPY hybrids were synthesised and characterised by NMR analysis and mass spectrometry. We measured their cytotoxic activity against cancer and normal cell lines, performed mechanistic studies by lipid peroxidation and determination of reduced (GSH) and oxidized (GSSG) glutathione, and imaged their subcellular localisation by confocal microscopy. Cell imaging experiments indicated that nor-β-lapachone-based BODIPY derivatives might preferentially localise in the lysosomes of cancer cells. These results assert the potential of hybrid quinone-BODIPY derivatives as promising prototypes in the search of new potent lapachone antitumor drugs.

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Synthesis and anti-Trypanosoma cruzi activity of derivatives from nor-lapachones and lapachones

Cited by 71 publications

References 26 publications

Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights

Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights

Screening for small molecule modulators of Hsp70 chaperone activity using protein aggregation suppression assays: inhibition of the plasmodial chaperone PfHsp70-1

On the synthesis of quinone-based BODIPY hybrids: New insights on antitumor activity and mechanism of action in cancer cells

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