Synthesis and preliminary pharmacological evaluation of new (±) 1,4-naphthoquinones structurally related to lapachol

Silva, Alcides J. M. da; Buarque, Camilla D.; Brito, Flávia V; Aurelian, Laure; Macedo, Luciana F.; Malkas, Linda H.; Hickey, Robert J.; Lopes, Daniele V.S; Noël, François; Murakami, Yugo L. B.; Silva, Noelson M.V; Melo, Paulo A.; Caruso, Rodrigo Rêgo Barros; Castro, Newton G.; Costa, Paulo R.R.

doi:10.1016/s0968-0896(02)00100-1

Cited by 78 publications

(29 citation statements)

References 33 publications

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“…All conjugates induced DNA fragmentation, a process that may involve ROS generation as suggested by data obtained with 5c. Our results corroborate work of other groups where modification of 1,4-naphthoquinones also induced increase in antitumoral activity reinforcing the importance of this approach for the development of more active drugs (28)(29)(30). Figure 6.…”

Section: Discussionsupporting

confidence: 90%

Antitumoral activity of new polyamine-naphthoquinone conjugates

Esteves-Souza

Lúcio²,

Cunha³

et al. 2008

Oncol Rep

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Abstract. Polyamine-naphthoquinone conjugates 5a-c were synthesized by nucleophilic displacement of 2-methoxylawsone 3a, 2-methoxylapachol 3b and 2-methoxy-norlapachol 3c with the polyamine N1-Boc-N5-Bn-spermidine 4. Unprotected derivatives 6a-c were synthesized to evaluate the effect of the protective Boc group on the activity of compounds 5a-c. The colorimetric MTT assay was used to evaluate their cytotoxic activity. All compounds were active against human lines of promyelocytic leukemia (HL-60), lung cancer (GLC4), Burkitt lymphoma (Daudi) and a mouse breast tumor (Ehrlich carcinoma), but only unprotected 6a-c showed activity against the human line of melanoma (MV-3). IC 50 values were obtained from dose response curves by linear regression. DNA fragmentation was measured by quantification of the subG1 peak of the cell cycle. Apoptosis of HL-60 treated with 5c was dose-dependent. The amount of DNA fragmentation observed by exposure of HL-60 to 25 μM of compounds 5a-c and 6a-c is compatible with the decrease in viability induced by the drugs at this concentration. Production of ROS was measured by H2-CFDA. Kinetics of HL-60 DNA fragmentation and ROS formation by 5c indicated that production of ROS precedes cell death. In conclusion, spermidine-1,4-naphthoquinone conjugates exhibited an increase in activity compared with the natural products and induced apoptosis of tumor cell lines by a mechanism that is mediated, at least in part, by ROS production.

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Section: Discussionsupporting

confidence: 90%

Antitumoral activity of new polyamine-naphthoquinone conjugates

Esteves-Souza

Lúcio²,

Cunha³

et al. 2008

Oncol Rep

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“…A solution of alkyl or aromatic hydrazide (5-100 mmol), 2-methyl- [1,4]naphthoquinone (1 equiv, 5-100 mmol) and a few drops of TFA was placed in a sealed tube in ethanol (10-50 ml) and stirred for 24 (or 72) hours at 90ºC. The reaction mixture was subsequently cooled to room temperature and the precipitate was filtered and washed with cold ethanol and dried in a vacuum oven at 50°C to afford the desired hydrazone as a solid.…”

Section: General Procedures For the Synthesis Of 6a-mmentioning

confidence: 99%

“…1 A multitude of naturally occurring naphthoquinones reportedly exhibit a diverse array of biological activities including fungicidal, 2 antibacterial, 3 antiviral, 4 antimalarial, 5 anticancer, 1,[6][7][8][9][10][11][12] in addition to effects that counter inflammation 13 and artherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological assessment of novel acylhydrazone derivatives of 2-methyl-1,4-naphthoquinone

Elaridi¹,

Bouhadi²,

Atallah³

et al. 2017

Org.Commun.

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Naphthoquinones are medicinally important molecules with a diverse array of biological properties such as antimicrobial, antifungal, antiviral, anti-inflammatory, anti-artherosclerotic and anticarcinogenic activities. In this study, we report the simple and direct preparation of a new group of novel menadione-hydrazone conjugates by reaction of 2-methyl-1,4-naphthoquinones with several aliphatic, aromatic and nucleobase hydrazides. The menadione-hydrazone conjugates were produced in excellent yields and characterized by IR, NMR and HRMS. The menadione derivatives were tested for their anticancer effects against human colon cancer HCT116 and human breast cancer MCF-7 cell lines. Interestingly, the molecules displayed disparate activities against both cell lines; the menadione hydrazones derived from the lipophilic myristic hydrazide and stearic hydrazide exhibited the most potent activity against HCT116 cell lines with IC50 of 89 and 64 μM. The most effective compounds against MCF-7 cells were the lauric hydrazide and benzoic hydrazide-derived menadione hydrazones with IC50 of 56 µM.

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“…The synthesis of these compounds has been the object of recent chemical studies (Claessens et al, 2010). Lapachol, the principal precursor of pyranonaphthoquinones and several compounds derived from lapachol have already been pharmacologically evaluated (Da Silva et al, 2002;Dos Santos et al, 2000;Guiraud et al, 1994), and found to exhibit a broad spectrum of biological activities (Eyong et al, 2008). Thus, derivatives from lapachol could be useful for the development of new drug candidates.…”

Section: Introductionmentioning

confidence: 99%

Cobalt mediated ring contraction reaction of lapachol and initial antibacterial evaluation of naphthoquinones derived from lapachol

et al. 2011

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The synthesis of 2-hydroxy-2-(3-methylbut-2-enyl)-2H-indene-1,3-dione 3, from lapachol which involves a ring contraction via the Hooker intermediate 1,2-dihydroxy-2-(3-methylbut-2-en-1-yl)-3-oxo-2,3-dihydro-1H-indene-1-carboxylic acid 2 is described. Different pyranonaphthoquinone derivatives, obtained in our previous synthetic work, were screened for antimycobacterial (Mycobacterium tuberculosis) activity and against resistant strains of Gram-positive (Bacillus cereus and Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The results indicated significant activity of all the tested samples against M. tuberculosis and only moderate activity against the Gram-positive and Gram-negative bacteria.

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Synthesis and preliminary pharmacological evaluation of new (±) 1,4-naphthoquinones structurally related to lapachol

Cited by 78 publications

References 33 publications

Antitumoral activity of new polyamine-naphthoquinone conjugates

Antitumoral activity of new polyamine-naphthoquinone conjugates

Synthesis and biological assessment of novel acylhydrazone derivatives of 2-methyl-1,4-naphthoquinone

Cobalt mediated ring contraction reaction of lapachol and initial antibacterial evaluation of naphthoquinones derived from lapachol

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