Molluscicidal activity of synthetic lapachol amino and hydrogenated derivatives

Silva, Tania M. S.; Câmara, Celso A.; Barbosa, Ticiano P.; Soares, André Z.; Cunha, Luciana C. da; Pinto, Ângelo C.; Vargas, Maria D.

doi:10.1016/j.bmc.2004.09.043

Cited by 86 publications

(43 citation statements)

References 20 publications

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“…The drugs used were: Cremophor The 3-hydroxy-4-(hydroxyimino)-2-(3-methylbut-2-enylnaphtalen-1(4H)-one) (Oxime S1, Figure 1) derivative of natural lapachol had its structure confirmed by infrared spectroscopy and mass spectrometry and was fully characterized by analytical and spectroscopic methods as earlier described [26]. Oxime S1 was dissolved in a mixture of distilled water and Chremophor.…”

Section: Drugs and Solutionsmentioning

confidence: 99%

Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway

et al. 2014

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It has been established that oximes cause endothelium-independent relaxation in blood vessels. In the present study, the cardiovascular effects of the new oxime 3-hydroxy-4-(hydroxyimino)-2-(3-methylbut-2-enylnaphtalen-1(4H)-one (Oxime S1) derived from lapachol were evaluated. In normotensive rats, administration of Oxime S1 (10,15, 20 and 30 mg/Kg, i.v.) produced dose-dependent reduction in blood pressure. In isolated aorta and superior mesenteric artery rings, Oxime S1 induced endothelium-independent and concentration-dependent relaxations (10 −8 M to 10 −4 M). In addition, Oxime S1-induced vasorelaxations were attenuated by hydroxocobalamin or methylene blue in aorta and by PTIO or ODQ in mesenteric artery rings, suggesting a role for the nitric oxide (NO) pathway. Additionally, Oxime S1 (30 and 100 µM) significantly increased NO concentrations (13.9 ± 1.6 nM and 17.9 ± 4.1 nM, respectively) measured by nitric oxide microsensors. Furthermore, pre-contraction with KCl (80 mM) prevented Oxime S1-derived vasorelaxation in endothelium-denuded aortic rings. Of note, combined treatment with potassium channel inhibitors also reduced Oxime S1-mediated vasorelaxation suggesting OPEN ACCESSMolecules 2014, 19 9774 a role for potassium channels, more precisely K ir , K v and K ATP channels. We observed the involvement of BK Ca channels in Oxime S1-induced relaxation in mesenteric artery rings.In conclusion, these data suggest that the Oxime S1 induces hypotension and vasorelaxation via NO pathway by activating soluble guanylate cyclase (sGC) and K + channels.

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Section: Drugs and Solutionsmentioning

confidence: 99%

Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway

et al. 2014

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“…O lapachol e todos os seus derivados (Figura 2) foram gentilmente cedidos pelo Prof. Celso Amorim Camara conforme procedimentos descritos na literatura (Barbosa, 2006;Barbosa-Filho et al, 2006;Camara et al, 2001;Camara et al, 2002;Silva et al, 2005).…”

Section: Methodsunclassified

“…Posteriormente o lapachol também foi encontrado em várias outras espécies como, por exemplo, no pau-d'arco-roxo (Tabebuia sp) (Fonseca et al, 2003). Neste trabalho estudamos o lapachol e seus derivados semi-sintéticos: -lapachona, -nor-lapachona, -lapachona, -nor-lapachona (Barbosa, 2006), 3-iodo--lapachona, 3-iodo--lapachona (Barbosa-Filho et al, 2006, assim como os derivados nitrogenados obtidos por semi-síntese, 2-amino- (Camara et al, 2001;Camara et al, 2002;Silva et al, 2005), e as imidas cíclicas que são substâncias similares ao alcalóide fi lantimida obtido de Phylanthus sellowianus (Euphorbiaceae) com importante atividade biológica (Figura 3) (Lima et al, 1999).…”

Section: Introductionunclassified

Atividade antimicrobiana "in vitro" e determinação da concentração inibitória mínina (CIM) de fitoconstituintes e produtos sintéticos sobre bactérias e fungos leveduriformes

Antunes¹,

Lima²,

Pereira³

et al. 2006

Rev. bras. farmacogn.

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RESUMO:Diante da problemática da resistência microbiana as pesquisas apontam para o uso de novos antibióticos que sejam efi cazes ante os patógenos emergentes. Este trabalho objetiva testar frente a bactérias gram-positivas (Staphylococcus aureus), bactérias gram-negativas (Escherichia coli e Pseudomonas aeruginosa) e fungos leveduriformes (Candida albicans), a atividade antimicrobiana e a concentração inibitória mínima (CIM) de fi toconstituintes de Ocotea duckei Vattimo, do lapachol, seus derivados semi-sintéticos, -lapachona, -nor-lapachona, -lapachona, -nor-lapachona, -3-iodo-lapachona e -3-iodo-lapachona, assim como 07 derivados nitrogenados obtidos a partir do lapachol por semi-síntese e de imidas cíclicas similares ao alcalóide fi lantimida. Os resultados obtidos estimulam o aprofundamento dos estudos para algumas dessas substâncias a exemplo do lapachol e seus análogos que demonstraram atividade antimicrobiana, de modo que os produtos que se apresentaram ativos para S. aureus, foram lapachol e o extrato etanólico de Ocotea duckei, para E. coli foi a iangambina e para a Candida albicans foram as imidas. As demais substâncias não apresentaram atividade antimicrobiana para as cepas testadas.Unitermos: Atividade antimicrobiana, fi toconstituintes, produtos de síntese, iangambina, lapachol, bactérias, leveduras.ABSTRACT: "In vitro antimicrobial activity and determination of the minimum inhibitory concentration (MIC) of natural and synthetic compounds against bacteria and leveduriform fungi". Regarding the problem of microbial resistance, the researches point to the use of new antibiotic which can be active against the emergent pathogens. This work aims to test the activity against Gram-positive bacteria (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli e Pseudomonas aeruginosa) and leveduriform fungi (Candida albicans), and also the Minimum Inhibitory Concentration (MIC) of the constituent of Ocotea duckei Vattimo, lapachol and its synthetic derivatives -lapachone, -nor-lapachone, -lapachone, -nor-lapachone, -3-iodinlapachone and -3-iodin-lapachone, as well as seven nitrogenated derivatives of lapachol obtained through semi synthesis. The achieved results stimulate the deepening of the studies for some of theses substances such as lapachol and its analogous which demonstrated antimicrobial activity. The substances which were active against S. aureus, were lapachol and the ethanolic extract of Ocotea duckei Vattimo, against Escherichia coli iangambin and against C. albicans the imides. The other substances did not show any activity against the tested bacteria.

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“…Polyamine-1,4-naphthoquinone conjugates 5a-c (14) were synthesized as follows: i) methylation of lapachol 2b and nor-lapachol 2c with dimethylsulphate in acetone and potassium carbonate, to yield 3b (77%) (15) and 3c (71%) (16), respectively, and synthesis of methoxylawsone (3a) from the sodium salt of 1,2-naphthoquinone-4-sulfonic acid (17); ii) preparation of the protected derivative of spermidine 4 in a four-step synthesis (18,19); iii) nucleophilic displacement of the methoxyquinones 3a-c with compound 4. To the solution 4 (110.0 mg; 0.40 mmol) in MeOH (2 ml) in a sealed tube, was added a solution of 3b (100.0 mg; 0.30 mmol) in MeOH (5 ml).…”

Section: Syntheses Of Polyamine-naphthoquinone Conjugates 5a-cmentioning

confidence: 99%

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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Molluscicidal activity of synthetic lapachol amino and hydrogenated derivatives

Cited by 86 publications

References 20 publications

Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway

Vasorelaxation Induced by a New Naphthoquinone-Oxime is Mediated by NO-sGC-cGMP Pathway

Atividade antimicrobiana "in vitro" e determinação da concentração inibitória mínina (CIM) de fitoconstituintes e produtos sintéticos sobre bactérias e fungos leveduriformes

Antitumoral activity of new polyamine-naphthoquinone conjugates

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