Chemical Reactivity Studies with Naphthoquinones from Tabebuia with Anti-trypanosomal Efficacy

Pinto, Cleverson N.; Dantas, Andrea P.; Moura, Kelly C. G. de; Emery, Flávio da Silva; Polequevitch, Pepita F.; Pinto, Maria do Carmo F. R.; Castro, Solange L. de; Pinto, Antônio V.

doi:10.1055/s-0031-1300337

Cited by 34 publications

(24 citation statements)

References 15 publications

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“…The UV-Vis spectra of the compounds obtained in CHCl 3 show two absorption bands. PBE1PBE/6-311+G(2d,p) calculations indicate that the band in the 275-290 nm region can be attributed to the aromatic and quinone p-p * transitions and the low-energy band in the visible region between 456 and 512 nm is attributed predominantly to p phenyl-p * naphthoquinone transitions.…”

Section: Uv-vis Spectramentioning

confidence: 99%

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Novel 2-(R-phenyl)amino-3-(2-methylpropenyl)-[1,4]-naphthoquinones: synthesis, characterization, electrochemical behavior and antitumor activity

Casellato¹,

Neves²,

Carneiro³

et al. 2010

J. Braz. Chem. Soc.

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Novas 2-(R-fenil)amino-3-(2-metilpropenil)-[1,4]-naftoquinonas (R = H, 4-OMe, 4-Ferrocenil, 4-Me, 3-Me, 4-I, 3-I, 4-CN, 3-CN, 4-NO 2 e 3-NO 2 ) derivadas do nor-lapachol [2-hidroxi-3-(2-metilpropenil)-1,4-naftoquinona] foram obtidas em bons rendimentos. A estrutura dos compostos foi proposta com base em estudos de difração de raios-X (R = OMe, 2b), dados de RMN de 1 H e 13 C e cálculos teóricos utilizando o funcional B3LYP e a base 6-311+G(2d,p). Os potenciais de meia-onda das aminonaftoquinonas e o deslocamento químico do hidrogênio da cadeia 3-propenil dos compostos 2a-k mostraram boa correlação com as constantes de Hammett dos substituintes presentes no anel fenileno. A avaliação da citotoxicidade evidenciou atividade antitumoral promissora para o substrato metóxi-nor-lapachol 1 e o derivado 4-ferrocenil 2c.Novel 2-(R-phenyl)amino-3-(2-methyl-propenyl)-[1,4]-naphthoquinones (R = H, 4-OMe, 4-Ferrocenyl, 4-Me, 3-Me, 4-I, 3-I, 4-CN, 3-CN, 4-NO 2 and 3-NO 2 ) derived from nor-lapachol [2-hydroxy-3-(2-methylpropenyl)-1,4-naphthoquinone] were obtained in good yields. Their structures were proposed on the basis of a single crystal X-ray diffraction study (R = OMe, 2b), 1 H and 13 C NMR studies and calculations using the B3LYP functional and the 6-311+G(2d,p) basis set. The half-wave potentials of the aminonaphthoquinones and 1 H NMR chemical shifts of the 3-propenyl hydrogen in 2a-k show good correlation with the substituent Hammett constants on the phenylamino ring. The antitumor assays showed promising activity for substrate methoxynor-lapachol 1 and the 4-ferrocenyl derivative 2c.Keywords: Nor-lapachol, arylamine, aminonaphthoquinone, electrochemistry, B3LYP, antitumor activity IntroductionNaphthoquinones are widely distributed in nature and some of these molecules have an important role in the biochemistry of microbial energy production, by means of photosynthesis and respiratory chain.1 Compounds containing the quinone group are known for exhibiting antitumor, 2 trypanocide, 3 moluscicide, 4 fungicide 5 and antimalarial 6 activities. The presence of an amino group in quinones has led to interesting biologically active compounds. 7-12Biological activity of quinones is often related to their electrochemical behavior. 13 The ability to accept one or two electrons to form the corresponding radical anion (Q •-) or dianion (Q 2-) species is believed to induce formation of reactive oxygen species, responsible for the oxidative stress in cells.14 The electron-accepting capacity of naphthoquinones may be tuned by carbonyl position changes (1,2-x 1,4-naphthoquinones) 15 or different substituents or functions attached to the naphthoquinone moiety, and the use of electrochemical methods to study Braz. Chem. Soc. 170 this type of molecules has proven to be useful. 16,17 We reported recently 18 the synthesis of a series of 2-arylamino-1,4-naphthoquinones from 2-methoxy-1,4-naphthoquinone and arylamines in the presence of MgCl 2• 6H 2 O and p-toluenesulfonic acid as catalysts. The reactions of both electron-donor and...

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Section: Uv-vis Spectramentioning

confidence: 99%

“…1 Compounds containing the quinone group are known for exhibiting antitumor, 2 trypanocide, 3 moluscicide, 4 fungicide 5 and antimalarial 6 activities. The presence of an amino group in quinones has led to interesting biologically active compounds.…”

Section: Introductionmentioning

confidence: 99%

Novel 2-(R-phenyl)amino-3-(2-methylpropenyl)-[1,4]-naphthoquinones: synthesis, characterization, electrochemical behavior and antitumor activity

Casellato¹,

Neves²,

Carneiro³

et al. 2010

J. Braz. Chem. Soc.

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“…Subsequently, it was washed with a 5 % solution of sodium metabisulfite to remove all aldehyde residues, followed by rinsing in water at 5°C until neutralization. The precipitate obtained was filtered, dried and purified by column chromatography on silica gel using a mixture of hexane/ethyl acetate as eluent and increasing the polarity gradient (Pinto et al 2000). The imidazole molecular structures are shown in Fig.…”

Section: Imidazoles Synthesismentioning

confidence: 99%

3-Indol carboxaldehyde, an imidazole synthesized from naphthoquinone β-lapachone downregulates Candida albicans biofilm

et al. 2014

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Candida species can cause infections that range from superficial to life-threatening events. Candida albicans is an opportunistic pathogen of human microbiota, and it is frequently described as a commensal organism, but in many cases, it can assume a pathogenic behavior. The increasing number of immunocompromised patients has promoted an increase in the incidence of microorganisms that are resistant to conventional therapy. Additionally, the limited number of antifungal drugs has made the search for new compounds extremely relevant. In this study, we determined the minimal inhibitory concentrations (MICs) of two synthetic imidazoles derived from b-lapachone, namely 3-indol carboxaldehyde and p-N(CH 3 )2-benzaldehyde against a clinical isolate of C. albicans resistant to fluconazole and the reference strain ATCC 10231. Both strains had their growth affected by 3-indol carboxaldehyde, and the MICs were calculated as 31.7 and 41 lg ml -1 for ATCC 10231 and the clinical isolate, respectively. However, the p-N(CH 3 )2-benzaldehyde MIC values were above 100 lg ml -1 for both strains. Morphogenesis assays revealed that 3-indol carboxaldehyde inhibited significantly the germ tube transformation process. Moreover, this azole was also able to interfere significantly with biofilm formation of both strains, and also demonstrated the ability to disaggregate mature biofilms. The results obtained in this study indicate that 3-indol carboxaldehyde may be considered a viable alternative in modulating C. albicans biofilm and viability.

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“…Quinones show several biological and pharmacological activities, [1][2][3][4][5][6][7][8][9] with their mechanism of action being related to redox cycling, which leads to the formation of reactive oxygen species that can damage cellular macromolecules. 10,11 The quinone cytotoxicity to many human cancer cell lines is amply recognized, [12][13][14][15][16][17] acting through inhibition of DNA repair enzymes, 18 inhibition or activation of DNA topoisomerase I, 17,19 induction of Vol.…”

Section: Introductionmentioning

confidence: 99%

The photochemical reactivity of triplet β-lapachone-3-sulfonic acid towards biological substrates

Netto‐Ferreira¹,

Lhiaubet‐Vallet²,

Silva³

et al. 2010

J. Braz. Chem. Soc.

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A reatividade fotoquímica do ácido 3-sulfônico da b-lapachona (1) frente a amino ácidos, bases nucleicas ou nucleosídeos foi determinada empregando a técnica de fotólise por pulso de laser de nanossegundo. A excitação (l = 355 nm) de soluções deaeradas de 1, em acetonitrila, resultou na formação do seu estado excitado triplete, o qual foi suprimido eficientemente por L-triptofano, éster metílico de L-triptofano, L-tirosina, éster metílico de L-tirosina e éster metílico de L-cisteína (k q ≅ 10 9 L mol -1 s -1). Para L-triptofano, L-tirosina e seus ésteres metílicos novos transientes foram formados no proceso de supressão, os quais foram atribuídos ao par de radicais resultante de uma transferência inicial de elétron do amino ácido, ou dos seus ésteres metílicos, à quinona excitada, seguida por uma transferência de próton rápida. Não foi possível a obtenção de constantes de velocidade de supressão para timina e timidina, em acetonitrila, o que pode ser devido tanto ao caráter p p* de 1 quanto ao baixo valor para a sua energia triplete. Por outro lado, a supressão de 1 por 2'-deoxaguanosina foi tão eficiente quanto para triptofano ou tirosina (k q ≅ 10 9 L mol -1 s -1). O rendimento quântico para a formação de oxigênio singlete ( 1 O 2 ) a partir de 1 foi determinado empregando-se estudos de emissão resolvida no tempo na região do infravermelho próximo, tendo-se obtido um valor consideravelmente alto para este rendimento quântico (F D = 0,7).The photochemical reactivity of b-lapachone-3-sulfonic acid (1) towards amino acids, nucleobases or nucleosides has been examined employing the nanosecond laser flash photolysis technique. Excitation (l = 355 nm) of degassed solutions of 1, in acetonitrile, resulted in the formation of its corresponding triplet excited state. This transient was efficiently quenched by L-tryptophan, L-tryptophan methyl ester, L-tyrosine, L-tyrosine methyl ester and L-cysteine methyl ester (k q ≅ 10 9 L mol -1 s -1). For L-tryptophan, L-tyrosine and their methyl esters new transients were formed in the quenching process, which were assigned to the corresponding radical pairs resulting from an initial electron transfer from the amino acids, or their esters, to the excited quinone, followed by a fast proton transfer. No measurable quenching rate constants could be observed in the presence of thymine or thymidine, in acetonitrile solution, which is probably due to the p p* character of triplet 1 as well as to its low triplet energy. On the other hand, the rate constant obtained when 1 was quenched by 2'-deoxyguanosine is reasonably fast (k q ≅ 10 9 L mol -1 s -1). The quantum efficiency of singlet oxygen ( 1 O 2 ) formation from 1 was determined employing time-resolved near-IR emission studies upon laser excitation and showed a considerably high value (F D = 0.7).Keywords: laser flash photolysis, ortho-quinones, triplet excited state, coupled electron/ proton transfer IntroductionQuinones show several biological and pharmacological activities, 1-9 with their mechanism of action being related to redo...

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Chemical Reactivity Studies with Naphthoquinones from Tabebuia with Anti-trypanosomal Efficacy

Cited by 34 publications

References 15 publications

Novel 2-(R-phenyl)amino-3-(2-methylpropenyl)-[1,4]-naphthoquinones: synthesis, characterization, electrochemical behavior and antitumor activity

Novel 2-(R-phenyl)amino-3-(2-methylpropenyl)-[1,4]-naphthoquinones: synthesis, characterization, electrochemical behavior and antitumor activity

3-Indol carboxaldehyde, an imidazole synthesized from naphthoquinone β-lapachone downregulates Candida albicans biofilm

The photochemical reactivity of triplet β-lapachone-3-sulfonic acid towards biological substrates

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