Caco-2 cells cytotoxicity of nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA)

Fernandes, Mariane B.; Gonçalves, José Eduardo; Scotti, Luciana; Oliveira, Alex Alfredo de; Tavares, Leoberto Costa; Storpirtis, Sílvia

doi:10.1016/j.tiv.2012.01.018

Cited by 17 publications

(11 citation statements)

References 26 publications

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“…Buisson et al confirm also that nifuroxazide, even in high dosage, does not affect microbial intestinal ecosystem. Importantly, nifuroxazide treatment does not induce cross-resistance to other antibacterial agents, including quinolones and sulfonamides, which indicates the possibility of its use in combined therapy of intestinal infections (1)(2)(3)(23)(24).…”

Section: Resultsmentioning

confidence: 99%

Safety of oral nifuroxazide – analysis of data from a spontaneous reporting system

Karłowicz-Bodalska¹,

Głowacka²,

Boszkiewicz³

et al. 2019

Acta Poloniae Pharmaceutica - Drug Research

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Nifuroxazide (4-hydroxy-benzoic acid; 2-[(5nitro-2-furanyl)methylene]hydrazide) is a chemotherapeutic agent belonging to the nitrofuran family. Indications for its use are acute and chronic bacterial diarrhea and other diseases with diarrhea (1). The drug has local antibacterial activity against some Gram-positive bacteria of the genus Staphylococcus and Gram-negative bacteria from the Enterobacteriaceae family: Yersinia spp., Escherichia spp., Enterobacter spp., Klebsiella spp. and Salmonella spp. It does not affect the bacteria Proteus vulgaris, Proteus mirabilis and Pseudomonas aeruginosa (1-3). Recently, attention has been paid to its antitumor potential in neuroblastoma, multiple myeloma, colorectal and breast cancer, efficacy in the treatment of graft-versus-host disease and nephroprotection in diabetes (4-10). The exact mechanism of action of nifuroxazide has not yet been identified. It probably has an inhibitory effect on dehydrogenase activity and protein synthesis in bacterial cells. Aldehyde dehydrogenase (ALDH) is responsible for the bioactivation of this prodrug. It has been found that nifuroxazide is a potent inhibitor of the Janus kinase 2 pathways and transcription factor 3 (JAK2/STAT3). It also has direct effects on oxidative stress and apoptosis (2, 4-6). Frequent self-administration of this drug by patients makes it necessary to pay attention to selfmedication, which in accordance with the guidelines of the World Health Organization is defined as ìusing medication by the consumer to treat signs/symptoms or minor health problems, recognized as such by themselvesî. In practice, this term also includes treatment by family members or friends, mainly, when the child is being treated (11). It should be responsible and safe, especially considering that diarrhea, in particular, acute diarrhea, is a serious problem of primary and hospital care. Itís serious complications, such as electrolyte disturbances, oligovolemic shock and even death, are dangerous especially for newborns, babies, small children and elderly people, due to their susceptibility to dehydration (12, 13). The fact that adverse effects inevitably accompany the desired therapeutic effects

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Section: Resultsmentioning

confidence: 99%

Safety of oral nifuroxazide – analysis of data from a spontaneous reporting system

Karłowicz-Bodalska¹,

Głowacka²,

Boszkiewicz³

et al. 2019

Acta Poloniae Pharmaceutica - Drug Research

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“…The optimization of available drugs is a financially accessible alternative that can provide promising antimicrobial agents [ 4 – 6 ]. Accordingly, in studies on novel drug development, research mostly concentrates on the chemical modification of the effective drugs or selected molecular structures to improve their bioavailability and potency, and consequently overcome antibiotic resistance mechanisms [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of New Fluoro-Benzimidazole Derivatives as an Approach towards the Discovery of Novel Intestinal Antiseptic Drug Candidates

Çevik

Sağlık

Özkay

et al. 2017

CPD

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In the present study, nineteen new fluoro-benzimidazole derivatives, including nifuroxazide analogs, were synthesized by microwave-supported reactions and tested against a panel of pathogenic microorganisms consisting of resistant strains. The synthesized compounds were characterized and identified by FT-IR, 1H- and 13C-NMR, mass spectroscopy, and elemental analyses, respectively. In vitro antimicrobial and cytotoxic effects of the synthesized compounds were determined by microdilution and by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. The compound 4-[5(6)-fluoro-1H-benzimidazol-2-yl)-N'-(2-methylbenzylidene)]benzohydrazide (18) showed particularly high inhibitory activity against the gastro-intestinal pathogens, such as Escherichia coli O157:H7, Escherichiacoli ATCC 8739, Escherichia coli ATCC 35218 and Salmonella typhimurium ATCC 13311 standard strains, with minimum inhibitory concentrations (MIC90) ranging from 0.49–0.98 µg/mL. The microbial panel contained a total of ten pathogens including Klebsiella sp., Mycobacterium sp., MRSA, etc., for which the level of inhibitory activity measured was higher than that exhibited by the tested concentrations (MIC > 1000 µg/mL). In vitro cytotoxicity results revealed that the inhibitory concentration (IC50) value (210.23 µg/mL) of compound 18 against CCD 841 CoN cells (human intestinal epithelial cell line) is about 430 times higher than its MIC90 value against the tested Escherichia coli strains. Furthermore, the docking study of compound 18 suggested that its structure is very compatible with the active site pocket of the phosphofructokinase-2 enzyme.

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“…Desta forma, observa que esta variação estrutural pode trazer benefícios no combate de micro-organismos. Diferença estrutural entre os derivados nitrocompostos.Estudos de citotoxicidade e permeabilidade celular de derivados da nifuroxazida realizados em nosso grupo de pesquisa(FERNANDES et al, 2012), demonstraram que os derivados nitrotiofênicos (figura 9) quando comparados aos seus análogos nitrofurânicos apresentaram menor toxicidade e melhor viabilidade celular. A partir deste trabalho, torna-se plausível supor que a toxicidade dos nitrocompostos è dependente de múltiplos fatores, como sua estrutura química, tempo de exposição e dose utilizada (SAPEL'NIKOVA et al, 2002;FERNANDES et al, 2012)…”

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“….Segundo FERNANDES e colaboradores, este tipo de comportamento dos derivados tiofênicos pode ser explicado pelo maior raio atômico do átomo de enxofre em comparação com o átomo de oxigênio. Dessa forma, a maior toxicidade dos derivados furânicos poderia estar associada ao átomo de oxigênio que, devido a sua maior capacidade de doar elétrons, poderia aumentar a reatividade do grupo nitro ligado ao anel furânico(FERNANDES et al, 2012).Bacillus subtilis(HOSSEINZADEH, et al, 2012) . Determinar a atividade antimicrobiana dos compostos obtidos frente às cepas selecionadas de micro-organismos causadores de infecções hospitalares.Para este trabalho foram planejados 24 compostos 5-nitrotiofilidênicos, sendo 12 derivados azometínicos (séria A) e 12 derivados oxadiaxolínicos (série B).…”

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Planejamento, síntese e avaliação da atividade de derivados 5-nitro-2-tiofilidênicos com estrutura azometínica e oxadiazolínica frente a micro-organismos causadores de infecções hospitalares

Bortolozzo¹

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Dedico este trabalho as pessoas que me ensinaram o sentido das palavras amor e simplicidade, aos meus avós Zoilo e Ercilia Bortolozzo que eu amo tanto. A minha alma gêmea Lucilia Vilela de Melo pelo companheirismo, cumplicidade, afeto, carinho, paciência e amor em todos os momentos. Agradecimentos A realização deste trabalho em muito se deve à colaboração e apoio de diversas pessoas, as quais transmito os mais sinceros agradecimentos: À Deus, em primeiro lugar, por me dar força, ânimo e sabedoria. Ao meu orientador, Prof. Dr. Leoberto Costa Tavares, pelos ensinamentos, amizade, apoio, respeito e incentivo em todos os momentos da realização desse trabalho. Agradeço a oportunidade que me foi dada. À amiga e Profa. Dra. Kerly Fernanda Mesquita Pasqualoto pela indicação ao LPDF, mas principalmente pela força e confiança depositada. Ao Dr. Salomão Dória Jorge, pela amizade, apoio, brincadeiras, ensinamentos e grande contribuição no desenvolvimento deste trabalho. À amiga e doutoranda Fanny Palace-Berl, pelo apoio, ensinamento e discussões de grande valor no desenvolvimento do trabalho. Ao companheiro de mestrado Rodrigo Rocha Zorzi, pelo auxílio constante, horas de conversas e pela convivência. Ao grande amigo Michael Jefferson Amorim de Oliveira, pelos muitos cafés expressos e conversas. Ao técnico João Sussumu Murayama, agradeço a atenção, disponibilidade e toda a ajuda prestada sempre que necessário. Aos amigos Adelson Neto e André Siqueira. À Prof. Dra. Marina Ishii pela doação de cepas microbiológicas utilizadas neste trabalho, pela amizade, atenção e ensinamentos. À Prof. Dra. Marina Baquerizo Martinez, Silvia Regina dos Santos e Cristiane Mika, pela doação das cepas de S. aureus ATCC 29213 e E.faecalis ATCC 29212 utilizada neste trabalho.

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Caco-2 cells cytotoxicity of nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA)

Cited by 17 publications

References 26 publications

Safety of oral nifuroxazide – analysis of data from a spontaneous reporting system

Safety of oral nifuroxazide – analysis of data from a spontaneous reporting system

Synthesis of New Fluoro-Benzimidazole Derivatives as an Approach towards the Discovery of Novel Intestinal Antiseptic Drug Candidates

Planejamento, síntese e avaliação da atividade de derivados 5-nitro-2-tiofilidênicos com estrutura azometínica e oxadiazolínica frente a micro-organismos causadores de infecções hospitalares

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