Structural and reactivity analyses of 2-benzylamino-1,4-naphthoquinone by X-ray characterization, electrochemical measurements, and dft single-molecule calculations

Cunha, Sílvio; Santos, Luis Fernandes P.; Rocha, Zildete; Rivelino, Roberto; Ferrari, Jailton; Vencato, Ivo; Lariucci, Carlito

doi:10.1590/s0100-40422010001000020

Cited by 5 publications

(5 citation statements)

References 20 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…II [37] and III [36] , [38] were prepared according to reported procedures. The novel synthetic route developed for the preparation of quinone-amino acid conjugates 1–15 is depicted in Figure 3 .…”

Section: Resultsmentioning

confidence: 99%

“…There are several reports on the use of this reaction to access 1,4-naphthoquinones possessing a substituted amino group in the 2-position [39] , [40] , [41] . However, especially for the transformation of less reactive anilines, catalysts [42] , high temperature [37] , and long reaction time [36] , [38] are often required. We developed a simple and straightforward experimental protocol which led to 19–21 in good yields and in parallel fashion.…”

Section: Resultsmentioning

confidence: 99%

“…In the anti-parasitic field, transporters have been much less exploited, even though a few have been showed to translocate Trypanosomatid-toxic compounds [47] . In Leishmania amino acid transporters play a major role in creating and maintaining intracellular pools of their corresponding substrates [38] . Hence, conjugating toxic drugs to Leishmania nutrients, which exploit specific amino acid transporters, might lead to successful approach for targeted toxicity.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Quinone-Amino Acid Conjugates Targeting Leishmania Amino Acid Transporters

et al. 2014

View full text Add to dashboard Cite

The aim of the present study was to investigate the feasibility of targeting Leishmania transporters via appropriately designed chemical probes. Leishmania donovani, the parasite that causes visceral leishmaniasis, is auxotrophic for arginine and lysine and has specific transporters (LdAAP3 and LdAAP7) to import these nutrients. Probes 1–15 were originated by conjugating cytotoxic quinone fragments (II and III) with amino acids (i.e. arginine and lysine) by means of an amide linkage. The toxicity of the synthesized conjugates against Leishmania extracellular (promastigotes) and intracellular (amastigotes) forms was investigated, as well their inhibition of the relevant amino acid transporters. We observed that some conjugates indeed displayed toxicity against the parasites; in particular, 7 was identified as the most potent derivative (at concentrations of 1 µg/mL and 2.5 µg/mL residual cell viability was reduced to 15% and 48% in promastigotes and amastigotes, respectively). Notably, 6, while retaining the cytotoxic activity of quinone II, displayed no toxicity against mammalian THP1 cells. Transport assays indicated that the novel conjugates inhibited transport activity of lysine, arginine and proline transporters. Furthermore, our analyses suggested that the toxic conjugates might be translocated by the transporters into the cells. The non-toxic probes that inhibited transport competed with the natural substrates for binding to the transporters without being translocated. Thus, it is likely that 6, by exploiting amino acid transporters, can selectively deliver its toxic effects to Leishmania cells. This work provides the first evidence that amino acid transporters of the human pathogen Leishmania might be modulated by small molecules, and warrants their further investigation from drug discovery and chemical biology perspectives.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Quinone-Amino Acid Conjugates Targeting Leishmania Amino Acid Transporters

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In the present work the synthesis of the 2-alkylamino-1,4-naphthoquinones was performed using two alternative methods, such as ultrasound (method A) 21,33 or microwave irradiation (method B). 1,4-Naphthoquinone and the appropriate amine were the starting material and ethanol was used as solvent.…”

Section: Synthesis and Antibacterial Assaysmentioning

confidence: 99%

Antibacterial Activity of 2-Amino-1,4-naphthoquinone Derivatives Against Gram‑Positive and Gram-Negative Bacterial Strains and Their Interaction with Human Serum Albumin

Silva

Chaves

Paiva

et al. 2020

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

A series of 2-amino-1,4-naphthoquinone derivatives (NQA-NQF) was synthesized by alternative methods (ultrasonication and microwave irradiation), with yields ranging from 40 to 71%, and without the need of further recrystallization. Each compound was evaluated against four Gram-positive (Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus and Bacillus cereus) and five Gram-negative (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae positive β-lactamase) bacteria strains. The NQF was the most active amino-naphthoquinone derivative with minimum inhibitory concentration (MIC) of 31.2 µg mL-1 against K. pneumoniae positive β-lactamase (a common intestinal bacteria which can cause life-threatening infections). On the other hand, NQA and NQC showed good activity as a potential antibiotic for the bacteria strains assayed, except for K. pneumoniae. In addition, the affinity of these three most active compounds (NQA, NQC, and NQF) for human serum albumin (HSA) was evaluated employing multiple spectroscopic techniques (steady-state, time-resolved, and synchronous fluorescence, as well as circular dichroism), combined with theoretical calculations (molecular docking). The interaction HSA:2-amino-1,4-naphthoquinones occurs spontaneously and moderately inside the subdomain IIA (Sudlow's site I) via hydrogen bonding and van der Waals forces.

show abstract

“…12 Recentemente, Cunha e colaboradores mostraram que a adição direta de benzilamina à 1,4-naftoquinona, em dimetilformamida, a temperatura ambiente, ocorre em rendimento moderado. 13 Valderrama e colaboradores empregaram ácido de Lewis como catalisador (CeCl 3 .7H 2 O, InBr 3 , FeCl 3 ) para obtenção de aminoisoquinolinas em rendimentos que variaram de acordo com a amina utilizada. 14 A água por ser o solvente universal, não ser inflamável e inofensiva ao meio ambiente tem muitas vantagens sobre os demais solventes orgânicos.…”

Section: Introductionunclassified

Adição de anilinas à naftoquinona em água e em fase sólida

Martinez¹,

Silva²,

Pinto³

et al. 2012

Quím. Nova

View full text Add to dashboard Cite

Recebido em 16/7/11; aceito em 30/9/11; publicado na web em 4/1/12 ADDITION OF AMINES TO NAPHTHOQUINONE IN WATER AND SOLID PHASE. Considering all the aspects of the principles of green chemistry, we present herein the addition reactions of amines to 1,4-naphthoquinone in water as solvent and also in solid phase. These reactions resulted in very colorful products that were easily monitored by thin layer chromatography and consequently easy to separate. Therefore, they are interesting experiments for experimental organic chemistry in the classrooms or in the laboratories.Keywords: naphthoquinone; anilines; green chemistry. INTRODUÇÃOSubstâncias contendo o núcleo quinona estão presentes em muitos produtos naturais, possuem um papel vital nos processos biológicos oxidativos, 1 e são de considerável importância na química medicinal, pois estão frequentemente associadas a várias atividades biológicas, como anticancerígena, 2 bactericida, 3 antimalárica, 4 tripanocida, 5 tuberculostática 6 e fungicida. 7A introdução de um grupo vicinal oxidável, como aminas substituídas, ao núcleo quinônico pode influenciar as propriedades redox do núcleo 2-amino-1,4-naftoquinona, e a literatura mostra que o esqueleto aminoquinona está presente em diversos derivados bioativos. 8A introdução de um grupo amino à posição C-2 da 1,4-naftoquinona envolve, usualmente, a adição de um grupo nitro, nitroso ou azida 9 com posterior redução desses grupos com hidretos metálicos ou reações de substituição nucleofílica de grupos metoxila 10 ou de átomos de halogênio no C-2.11 O acoplamento oxidativo de alquil ou arilaminas à 1,4-naftoquinona ocorre em uma única etapa, é simples, rápido e de fácil execução.Em trabalhos anteriores, nosso grupo de pesquisa desenvolveu um protocolo empregando ultrassom para a preparação de 2-aminocarboidratos-1,4-naftoquinonas em bons rendimentos e em curto tempo de reação.12 Recentemente, Cunha e colaboradores mostraram que a adição direta de benzilamina à 1,4-naftoquinona, em dimetilformamida, a temperatura ambiente, ocorre em rendimento moderado.13 Valderrama e colaboradores empregaram ácido de Lewis como catalisador (CeCl 3 .7H 2 O, InBr 3 , FeCl 3 ) para obtenção de aminoisoquinolinas em rendimentos que variaram de acordo com a amina utilizada. 14 A água por ser o solvente universal, não ser inflamável e inofensiva ao meio ambiente tem muitas vantagens sobre os demais solventes orgânicos. Entretanto, a sua diferença de polaridade em relação aos reagentes orgânicos apolares a torna menos utilizada em reações químicas, devido à menor solubilidade de muitos compostos orgânicos em água. Contudo, nos últimos anos o uso da água como solvente em reações orgânicas vem aumentado consideravelmente. 15Entre as muitas classes de reações que podem ser feitas usando como solvente a água, pode-se destacar as reações de adição nucleofílica do tipo Michael. 16Nos cursos de Química e de áreas afins é cada vez mais importante conscientizar os estudantes da necessidade de se desenvolver processos químicos que não agridam ao meio ambie...

show abstract

Structural and reactivity analyses of 2-benzylamino-1,4-naphthoquinone by X-ray characterization, electrochemical measurements, and dft single-molecule calculations

Cited by 5 publications

References 20 publications

Quinone-Amino Acid Conjugates Targeting Leishmania Amino Acid Transporters

Quinone-Amino Acid Conjugates Targeting Leishmania Amino Acid Transporters

Antibacterial Activity of 2-Amino-1,4-naphthoquinone Derivatives Against Gram‑Positive and Gram-Negative Bacterial Strains and Their Interaction with Human Serum Albumin

Adição de anilinas à naftoquinona em água e em fase sólida

Contact Info

Product

Resources

About