A Quinoxaline Derivative as a Potent Chemotherapeutic Agent, Alone or in Combination with Benznidazole, against Trypanosoma cruzi

Rodrigues, Jean Henrique da Silva; Ueda-Nakamura, Tânia; Corrêa, Arlene G.; Sangi, Diego Pereira; Nakamura, Celso Vataru

doi:10.1371/journal.pone.0085706

Cited by 50 publications

(44 citation statements)

References 53 publications

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“…Thus, PI labeling was absent in treated cells, indicating that the cell membrane was intact after treatment. This was also seen with T. cruzi epimastigotes treated with LSPN337 (33).…”

Section: Discussionmentioning

confidence: 60%

“…The data on the cytotoxicities of both compounds for J774-A1 macrophages and LLCMK 2 cells indicated that they had lower cytotoxicities than amphotericin B and miltefosine. In addition to the evaluation of in vitro cytotoxicity, the evaluation of hemolytic activity is also important when the safety of specific compounds is investigated (33). Here the hemolytic activity was Ͻ0.5% for both LSPN329 and LSPN331 at the highest concentration of each compound tested in our experiments.…”

Section: Discussionmentioning

confidence: 80%

“…An alteration of the cell volume was also revealed by SEM. Just as with 2,3-diarylsubstituted quinoxalines, the compound 3-chloro-7-methoxy-2-(methylsulfonyl)quinoxaline (LSPN337) caused changes in cell volume in epimastigotes of T. cruzi only at higher concentrations (33).…”

Section: Discussionmentioning

confidence: 99%

“…The antileishmanial activities of the quinoxaline derivatives 4-alkapolynylpyrrolo[1,2-␣]quinoxalines (29,30) and 1,4-di-N-oxide quinoxaline (13,26,31,32) have also been reported. We recently reported the activity of 2,3-disubstituted quinoxaline derivatives against Trypanosoma cruzi and L. amazonensis (33,34).…”

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confidence: 99%

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In Vitro and In Vivo Activities of 2,3-Diarylsubstituted Quinoxaline Derivatives against Leishmania amazonensis

Kaplum

Cogo

Sangi

et al. 2016

Antimicrob Agents Chemother

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Leishmaniasis is endemic in 98 countries and territories worldwide. The therapies available for leishmaniasis have serious side effects, thus prompting the search for new therapies. The present study investigated the antileishmanial activities of 2,3-diarylsubstituted quinoxaline derivatives against Leishmania amazonensis. The antiproliferative activities of 6,7-dichloro-2,3-diphenylquinoxaline (LSPN329) and 2,3-di-(4-methoxyphenyl)-quinoxaline (LSPN331) against promastigotes and intracellular amastigotes were assessed, and the cytotoxicities of LSPN329 and LSPN331 were determined. Morphological and ultrastructural alterations were examined by electron microscopy, and biochemical alterations, reflected by the mitochondrial membrane potential (⌬⌿m), mitochondrial superoxide anion (O 2 · ؊ ) concentration, the intracellular ATP concentration, cell volume, the level of phosphatidylserine exposure on the cell membrane, cell membrane integrity, and lipid inclusions, were evaluated. In vivo antileishmanial activity was evaluated in a murine cutaneous leishmaniasis model. Compounds LSPN329 and LSPN331 showed significant selectivity for promastigotes and intracellular amastigotes and low cytotoxicity. In promastigotes, ultrastructural alterations were observed, including an increase in lipid inclusions, concentric membranes, and intense mitochondrial swelling, which were associated with hyperpolarization of ⌬⌿m, an increase in the O 2 · ؊ concentration, decreased intracellular ATP levels, and a decrease in cell volume. Phosphatidylserine exposure and DNA fragmentation were not observed. The cellular membrane remained intact after treatment. Thus, the multifactorial response that was responsible for the cellular collapse of promastigotes was based on intense mitochondrial alterations. BALB/c mice treated with LSPN329 or LSPN331 showed a significant decrease in lesion thickness in the infected footpad. Therefore, the antileishmanial activity and mitochondrial mechanism of action of LSPN329 and LSPN331 and the decrease in lesion thickness in vivo brought about by LSPN329 and LSPN331 make them potential candidates for new drug development for the treatment of leishmaniasis.

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“…Thus, PI labeling was absent in treated cells, indicating that the cell membrane was intact after treatment. This was also seen with T. cruzi epimastigotes treated with LSPN337 (33).…”

Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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In Vitro and In Vivo Activities of 2,3-Diarylsubstituted Quinoxaline Derivatives against Leishmania amazonensis

Kaplum

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Sangi

et al. 2016

Antimicrob Agents Chemother

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“…Estas drogas podem curar com êxito, aproximadamente, 20% a 80% de pacientes com doença de Chagas aguda, porém existem reações adversas como anorexia, náuseas, desordens psicológicas, polineuropatias e dermatitis, advindas do uso destas drogas (Rodrigues et al, 2014). Desta forma, devido às limitações dos medicamentos disponíveis para o tratamento da Doença de Chagas e os inúmeros efeitos colaterais por eles demonstrados, vê-se a necessidade de investigação de novos princípios ativos, mais eficazes e menos tóxicos.…”

Section: Introductionunclassified

Avaliação das atividades antibacteriana, tripanocida e citotóxica do extrato hidroalcóolico das raízes de Tradescantia sillamontana Matuda (Veludo Branco) (Commelinaceae)

Estevam

Silva

Miranda

et al. 2016

Rev. bras. plantas med.

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RESUMO:O objetivo deste estudo foi avaliar o efeito antibacteriano e tripanocida in vitro do extrato hidroalcóolico das raízes de Tradescantia sillamontana Matuda (Commelinaceae), conhecida popularmente como veludo branco. Foi avaliada a atividade antibacteriana in vitro frente às bactérias Streptococcus mitis (CIM = 100 µg/mL; CMB = 150 µg/mL), Streptococcus mutans (CIM = 200 µg/mL; CMB = 220 µg/mL), Streptococcus sanguinis (CIM = 400 µg/mL; CMB = 425 µg/mL), Streptococcus sobrinus (CIM = 400 µg/mL; CMB = 420 µg/mL) e Bacteroides fragilis (CIM = 400 µg/mL; CMB = 430 µg/mL) pelo método de diluição em caldo. Os protozoários da família tripanossomatídeo causam doenças tropicais que costumam ser negligenciadas que costumam ser como a tripanossomíase, para a qual estão disponíveis poucos medicamentos. Neste contexto, o extrato hidroalcóolico das raízes de T. sillamontana também foi avaliado frente às formas tripomastigotas da cepa Y de Trypanosoma cruzi, com promissora atividade frente a este protozoário (IC 50 = 2,4 µg/mL). Quando avaliada a atividade citotóxica frente a fibroblastos da linhagem LLCMK 2 , o extrato apresentou moderada citotoxicidade (CC 50 = 480,37 µg/mL). Os resultados ora apresentados para o extrato hidroalcóolico das raízes de Tradescantia sillamontana Matuda demonstraram promissoras atividades antibacteriana e tripanocida, sendo uma fonte alternativa de produtos naturais com atividades contra T. cruzi e algumas bactérias do gênero Streptococcus e Bacteroides. Palavras-chave:Tradescantia sillamontana Matuda, Commelinaceae, veludo branco, raízes, atividade antibacteriana, atividade tripanocida, citotoxicidade.ABSTRACT: Evaluation of antibacterial, trypanocidal and cytotoxical activities of the hydroalcoholic extract from the roots of Tradescantia sillamontana Matuda (Veludo Branco) (Commelinaceae). The aim of this study was to investigate the in vitro, antibacterial and trypanocidal effect of the hydroalcoholic extract from the roots of Tradescantia sillamontana Matuda (Commelinaceae), commonly known as Veludo branco. The in vitro antibacterial activity against the standard bacteria Streptococcus mitis (MIC = 100µg/mL; MBC = 150 µg/ mL), Streptococcus mutans (MIC = 200µg/mL; MBC = 220 µg/mL), Streptococcus sanguinis (MIC = 400µg/mL; MBC = 425 µg/mL), Streptococcus sobrinus (MIC = 400µg/mL; MBC = 420 µg/mL) andBacteroides fragilis (MIC = 400µg/mL; MBC = 430 µg/mL), using microdilution broth methods. Protozoans from the trypanosomatid family cause neglected tropical diseases such as trypanosomiasis, for which few drugs are available. In this context, the hydroalcoholic extract of the Tradescantia sillamontana roots was also investigated with regards to the in vitro effects against the trypomastigote forms of theY strain of Trypanosoma cruzi, showing strong activity against this parasite (IC 50 = 2.4 µg/mL). When performing cytotoxic activity against fibroblasts LLCMK 2 line, the extract showed moderate cytotoxicity (CC 50 = 480.37 mg/mL).

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Compounds Containing 2,3‐Bis(phenylamino) Quinoxaline Exhibit Activity Against Methicillin‐Resistant Staphylococcus aureus, Enterococcus faecalis, and Their Biofilms

Padalino,

Duggan,

Mur

et al. 2024

MicrobiologyOpen

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Antimicrobial resistance remains a global issue, hindering the control of bacterial infections. This study examined the antimicrobial properties of 2,3‐N,N‐diphenyl quinoxaline derivatives against Gram‐positive, Gram‐negative, and Mycobacterium species. Two quinoxaline derivatives (compounds 25 and 31) exhibited significant activity against most strains of Staphylococcus aureus, Enterococcus faecium, and Enterococcus faecalis tested, with MIC values ranging from 0.25 to 1 mg/L. These compounds also showed effective antibacterial activity against methicillin‐resistant S. aureus (MRSA) and vancomycin‐resistant E. faecium/E. faecalis (VRE) strains. They demonstrated comparable or superior activity to four current antibiotics (vancomycin, teicoplanin, daptomycin, and linezolid) against a wide range of clinically relevant isolates. Additionally, they were more effective in preventing S. aureus and E. faecalis biofilm formation compared to several other antibiotics. In summary, these two quinoxaline derivatives have potential as new antibacterial agents.

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A Quinoxaline Derivative as a Potent Chemotherapeutic Agent, Alone or in Combination with Benznidazole, against Trypanosoma cruzi

Cited by 50 publications

References 53 publications

In Vitro and In Vivo Activities of 2,3-Diarylsubstituted Quinoxaline Derivatives against Leishmania amazonensis

In Vitro and In Vivo Activities of 2,3-Diarylsubstituted Quinoxaline Derivatives against Leishmania amazonensis

Avaliação das atividades antibacteriana, tripanocida e citotóxica do extrato hidroalcóolico das raízes de Tradescantia sillamontana Matuda (Veludo Branco) (Commelinaceae)

Compounds Containing 2,3‐Bis(phenylamino) Quinoxaline Exhibit Activity Against Methicillin‐Resistant Staphylococcus aureus, Enterococcus faecalis, and Their Biofilms

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