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BACKGROUND: Triamterene is an oral antihypertensive drug with dissolution-limited poor bioavailability. It can be used as monotherapy or in fixed dose combination with hydrochlorothiazide which also suffers from poor dissolution. Moreover, co-processing of drugs in fixed dose combination can alter their properties. Accordingly, pre-formulation studies should investigate the effect of co-processing and optimize the dissolution of drugs before and after fixed dose combination. This is expected to avoid deleterious interaction (if any) and to hasten the biopharmaceutical properties. OBJECTIVE: Accordingly, the aim of this work was to optimize the dissolution rate of triamterene alone and after fixed dose combination with hydrochlorothiazide. METHODOLOGY: Triamterene was subjected to dry co-grinding with xylitol, HPMC-E5 or their combination. The effect of co-grinding with hydrochlorothiazide was also tested in absence and presence of xylitol and HPMC-E5. The products were assessed using Fourier-transform infrared (FTIR), differential scanning calorimetry, X-ray powder diffraction (XRPD), in addition to dissolution studies. Optimum formulations were fabricated as oral disintegrating tablets (ODT).Results: Co-processing of triamterene with xylitol formed eutectic system which hastened dissolution rate. HPMC-E5 resulted in partial amorphization and improved triamterene dissolution. Co-grinding with both materials combined their effects. Co-processing of triamterene with hydrochlorothiazide resulted in eutexia but the product was slowly dissolving due to aggregation. This problem was vanished in presence of HPMC-E5 and xylitol. Compression of the optimum formulation into ODT underwent fast disintegration and liberated acceptable amounts of both drugs. CONCLUSION: The study introduced simple co-processing with traditional excipients for development of ODT of triamterene and hydrochlorothiazide.
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Hidroclorotiazida , Triantereno , Hidroclorotiazida/química , Xilitol , Anti-Hipertensivos/química , Comprimidos/química , SolubilidadeRESUMO
Mucopolysaccharidosis I-Hurler (MPS I-H) is caused by the loss of α-L-iduronidase, a lysosomal enzyme that degrades glycosaminoglycans. Current therapies cannot treat many MPS I-H manifestations. In this study, triamterene, an FDA-approved, antihypertensive diuretic, was found to suppress translation termination at a nonsense mutation associated with MPS I-H. Triamterene rescued enough α-L-iduronidase function to normalize glycosaminoglycan storage in cell and animal models. This new function of triamterene operates through premature termination codon (PTC) dependent mechanisms that are unaffected by epithelial sodium channel activity, the target of triamterene's diuretic function. Triamterene represents a potential non-invasive treatment for MPS I-H patients carrying a PTC.
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Mucopolissacaridose I , Animais , Mucopolissacaridose I/genética , Iduronidase , Triantereno , Códon sem Sentido , Diuréticos , Glicosaminoglicanos/metabolismoRESUMO
The formation of inclusion complexes between triamterene (TT) and cyclodextrins (CDs) to increase the water apparent solubility of TT was investigated. UV data showed that the binding constant of the TT/sulfobutylether-ß-cyclodextrin (SBE-ß-CD) inclusion complex was 510 L/mol. The phenyl ring of TT was inserted into the secondary hydroxy face of SBE-ß-CD, as demonstrated by 1H-1H rotating frame nuclear Overhauser effect spectroscopy NMR. Physicochemical properties of solid TT/SBE-ß-CD complexes prepared by physical mixing, kneading, freeze-drying, and mechanochemical methods were studied by X-ray diffraction and 13C cross-polarization and magic angle spinning NMR. With the mechanochemical method, the diffraction peak corresponding to TT disappeared, indicating the formation of an inclusion complex. The results of the dissolution test revealed that the solid complex obtained by the mechanochemical method improved the dissolution of TT. The water apparent solubility of TT can be improved by simple mechanical mixing without organic solvents, and improved bioavailability after oral administration is expected.
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Ciclodextrinas , beta-Ciclodextrinas , Varredura Diferencial de Calorimetria , Liofilização , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Triantereno , Difração de Raios XRESUMO
The purpose of this study was to prepare solid dispersions of triamterene (TRT) with ascorbic acid (AA) or ascorbic acid 2 glucoside (AA2G) and to evaluate their physical properties. Solid dispersions were prepared by dissolving each sample in an organic solvent and evaporation (EVP). Powder X-ray diffraction (PXRD) revealed a halo pattern for EVP1 (AA/TRT = 1/1) and EVP2 (AA2G/TRT = 1/1). In differential scanning calorimetry (DSC), endothermic peaks due to the melting of TRT and AA disappeared for EVP1 (AA/TRT = 1/1), and the melting peaks of TRT and AA2G disappeared for EVP2 (AA2G/TRT = 1/1). Fourier transform infrared (FT-IR) spectroscopy revealed broadened peaks for EVP1 (AA/TRT = 1/1) and EVP2 (AA2G/TRT = 1/1) due to the hydroxyl groups (-OH) of AA and the amino groups (-NH2) of TRT and also revealed a peak shift due to the pteridine skeleton (C = N) of TRT. In near-infrared absorption (NIR) spectroscopy, peaks due to the hydroxyl groups (-OH) of AA and AA2G were found for EVP1 (AA/TRT = 1/1) and EVP2 (AA2G/TRT = 1/1), respectively. A peak due to the amino groups (-NH2) was evident. This suggested the formation of an evaporation, in which TRT interacted with AA or AA2G. In the dissolution test, the dissolved fraction of TRT alone after 3 min was 30%, whereas the fractions were enhanced to approximately 90% for EVP1 (AA/TRT = 1/1) and EVP2 (AA2G/TRT= 1/1). Results confirmed that dissolution properties were improved as a result of complex formation. The above findings indicated improvement the dissolution properties of TRT.
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Ácido Ascórbico , Triantereno , Varredura Diferencial de Calorimetria , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
Sensitive, simple and specific spectrophotometric and spectrofluorimetric methods were developed for the determination of triamterene in bulk powder and pharmaceutical dosage form. The spectrophotometric method (Method A) is based on the formation of an ion-pair complex with eosin Y in acetate buffered solution of pH 3.7 followed by measuring the absorbance at 545 nm. The absorbance-concentration plot is rectilinear over the range 3.0-15.0 µg/mL with a limit of detection (LOD) of 0.429 µg/mL and a limit of quantitation (LOQ) of 1.031 µg/mL. The spectrofluorimetric method (Method B) is based on the reaction of triamterene with 7- chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in basic solution (pH 10) to form a product with high fluorescence measured at 546 nm after being excited at 438 nm. The plot of fluorescence versus concentration is linear within the range 2.0-10.0 µg/mL. The suggested methods were applied for the analysis of commercial capsules containing the studied drug with successful results. The results obtained from the proposed method were statistically compared with those of a reported one and revealed good agreement. The presented methods are useful in routine analysis of triamterene in laboratories of quality control.
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Triantereno/análise , Cápsulas/química , Estrutura Molecular , Pós/química , Espectrometria de Fluorescência , EspectrofotometriaRESUMO
Diuretic resistance is defined as a failure to achieve the therapeutically desired reduction in edema despite a full dose of diuretic. The causes of diuretic resistance include poor adherence to drug therapy or dietary sodium restriction, pharmacokinetic issues, and compensatory increases in sodium reabsorption in nephron sites that are not blocked by the diuretic. To illustrate the pathophysiology and management of diuretic resistance, we describe a patient with nephrotic syndrome. This patient presented with generalized pitting edema and weight gain despite the use of oral loop diuretics. Nephrotic syndrome may cause mucosal edema of the intestine, limiting the absorption of diuretics. In addition, the patient's kidney function had deteriorated, impairing the tubular secretion of diuretics. He was admitted for intravenous loop diuretic treatment. However, this was ineffective, likely due to compensatory sodium reabsorption by other tubular segments. The combination of loop diuretics with triamterene, a blocker of the epithelial sodium channel, effectively reduced body weight and edema. Recent data suggest that plasmin in nephrotic urine can activate the epithelial sodium channel, potentially contributing to the diuretic resistance in this patient. This case is used to illustrate and review the mechanisms of, and possible interventions for, diuretic resistance.
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Edema/tratamento farmacológico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Resistência a Medicamentos , Edema/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/complicações , Falha de TratamentoRESUMO
This paper reports the applicability of two-phase and three-phase hollow fiber based liquid-phase microextraction (HF-LPME) for the extraction of hydrochlorothiazide (HYD) and triamterene (TRM) from human urine. The HYD in two-phase HF-LPME is extracted from 24 mL of the aqueous sample into an organic phase with microliter volume located inside the pores and lumen of a polypropylene hollow fiber as acceptor phase, but the TRM in three-phase HF-LPME is extracted from aqueous donor phase to organic phase and then back-extracted to the aqueous acceptor phase, which can be directly injected into HPLC for analysis. Under optimized conditions preconcentration factors of HYD and TRM were obtained as 128 and 239, respectively. The calibration curves were linear (R(2) ≥ 0.995) in the concentration range of 1.0-100 µg/L for HYD and 2.0-100 µg/L for TRM. The limits of detection for HYD and TRM were 0.5 µg/L. The intra-day and inter-day RSD based on four replicates were obtained as ≤5.8 and ≤9.3%, respectively. The methods were successfully applied for determining the concentration of the drugs in urine samples. Copyright © 2015 John Wiley & Sons, Ltd.
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Diuréticos/isolamento & purificação , Hidroclorotiazida/isolamento & purificação , Microextração em Fase Líquida/métodos , Triantereno/isolamento & purificação , Diuréticos/urina , Humanos , Hidroclorotiazida/urina , Triantereno/urinaRESUMO
Medications can cause a tubulointerstitial insult leading to acute kidney injury through multiple mechanisms. Acute tubular injury, a dose-dependent process, occurs due to direct toxicity on tubular cells. Acute interstitial nephritis characterized by interstitial inflammation and tubulitis develops from drugs that incite an allergic reaction. Other less common mechanisms include osmotic nephrosis and crystalline nephropathy. The latter complication is rare but has been associated with several drugs, such as sulfadiazine, indinavir, methotrexate, and ciprofloxacin. Triamterene crystalline nephropathy has been reported only rarely, and its histologic characteristics are not well characterized. We report 2 cases of triamterene crystalline nephropathy, one of which initially was misdiagnosed as 2,8-dihydroxyadenine crystalline nephropathy.
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Hidroclorotiazida/efeitos adversos , Rim/patologia , Insuficiência Renal Crônica , Triantereno/efeitos adversos , Suspensão de Tratamento , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Biópsia , Creatinina/sangue , Erros de Diagnóstico/prevenção & controle , Combinação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Imunofluorescência , Taxa de Filtração Glomerular , Humanos , Hidroclorotiazida/administração & dosagem , Síndrome de Liddle/tratamento farmacológico , Doença de Meniere/tratamento farmacológico , Pessoa de Meia-Idade , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Resultado do Tratamento , Triantereno/administração & dosagemRESUMO
Due to the potential benefits of triamterene in diuretic resistance, this study was performed to assess whether triamterene add-on to the standard treatment of heart failure (HF)-related diuretic resistance improves outcomes. A randomized clinical trial was performed on 45 hospitalized patients with HF with reduced ejection fraction who had diuretic resistance. Patients were randomized to receive either triamterene 50 mg plus hydrochlorothiazide 25 mg (n = 23) or hydrochlorothiazide 50 mg alone (n = 22) until hospital discharge. The primary outcomes were changes in weight and fluid input-to-output ratio. Secondary outcomes were respiratory rate, hospitalization duration, serum sodium and potassium, estimated glomerular filtration rate, creatinine, and blood urea nitrogen levels during the study period. The mean (standard deviation) of weight changes was not significantly different in the intervention and the control groups (-6.3 [4.8] vs -4.8 [2.4] kg, respectively; P = .1). No significant differences were shown in input-to-output changes between the 2 groups (208.0 [243.4] in the intervention and 600.2 [250.3] in the control group; P = .4). Although the respiratory rate of triamterene-treated patients decreased, the difference did not reach statistical significance (P = .2). Other secondary outcomes were also similar in both groups. This study did not support the use of triamterene as an add-on therapy for patients with HF-related diuretic resistance.
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Diuréticos , Insuficiência Cardíaca , Humanos , Diuréticos/uso terapêutico , Triantereno/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Hidroclorotiazida/uso terapêutico , Potássio/uso terapêuticoRESUMO
PURPOSE: Cisplatin is the core chemotherapeutic drug used for first-line treatment of advanced non-small cell lung cancer (NSCLC). However, drug resistance is severely hindering its clinical efficacy. This study investigated the circumvention of cisplatin resistance by repurposing non-oncology drugs with putative histone deacetylase (HDAC) inhibitory effect. METHODS: A few clinically approved drugs were identified by a computational drug repurposing tool called "DRUGSURV" and evaluated for HDAC inhibition. Triamterene, originally indicated as a diuretic, was chosen for further investigation in pairs of parental and cisplatin-resistant NSCLC cell lines. Sulforhodamine B assay was used to evaluate cell proliferation. Western blot analysis was performed to examine histone acetylation. Flow cytometry was used to examine apoptosis and cell cycle effects. Chromatin immunoprecipitation was conducted to investigate the interaction of transcription factors to the promoter of genes regulating cisplatin uptake and cell cycle progression. The circumvention of cisplatin resistance by triamterene was further verified in a patient-derived tumor xenograft (PDX) from a cisplatin-refractory NSCLC patient. RESULTS: Triamterene was found to inhibit HDACs. It was shown to enhance cellular cisplatin accumulation and potentiate cisplatin-induced cell cycle arrest, DNA damage, and apoptosis. Mechanistically, triamterene was found to induce histone acetylation in chromatin, thereby reducing the association of HDAC1 but promoting the interaction of Sp1 with the gene promoter of hCTR1 and p21. Triamterene was further shown to potentiate the anti-cancer effect of cisplatin in cisplatin-resistant PDX in vivo. CONCLUSION: The findings advocate further clinical evaluation of the repurposing use of triamterene to overcome cisplatin resistance.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidores de Histona Desacetilases/farmacologia , Triantereno/farmacologia , Triantereno/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Histonas/metabolismo , Reposicionamento de Medicamentos , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Histona Desacetilases , Histona Desacetilase 1/metabolismo , Histona Desacetilase 1/farmacologiaRESUMO
Urine is one of the most used biological fluids for screening drug delivery and the resultant metabolites. In sports, the use of diuretics such as triamterene is considered a violation of anti-doping rules and is stipulated to be present at less than 79 nM in urine by the World Anti-Doping Agency (WADA). It is therefore important to develop effective rapid and low-cost tests for this diuretic. Here we apply electrochemical analysis using boron-doped diamond (BDD) electrodes, which have superior properties such as low background current, a wide potential window, and high resistance to deactivation. Since real urine samples show clear oxidation current peaks in the potential range more positive than 0.5 V (vs. Ag/AgCl) due to the presence of bio-components such as protein, uric acid, and ascorbic acid, to detect triamterene effectively, the electrochemical protocol was optimized towards a potential range where the other components have limited effect. Our results show that reduced triamterene exhibits an oxidation peak at 0.1 V (vs. Ag/AgCl) in 0.1 M phosphate buffer (PB) and at 0.2 V (vs. Ag/AgCl) in pooled human urine. The peak current value increased according to the triamterene concentration. The limit of detection (LOD) was 3.15 nM in the PB and 7.80 nM in pooled human urine. Finally, triamterene detection was attempted in individual urine samples. Triamterene was electrochemically detectable in individual urine samples, excluding urine samples containing an excess amount of ascorbic acid. The limit of detection (LOD) in individual urine samples was determined to be 20.8 nM.
Assuntos
Técnicas Biossensoriais , Boro , Ácido Ascórbico , Boro/química , Diuréticos , Eletrodos , Humanos , Indicadores e Reagentes , Fosfatos , Triantereno , Ácido ÚricoRESUMO
The maintenance of lysosomal integrity is essential for lysosome function and cell fate. Damaged lysosomes are degraded by lysosomal autophagy, lysophagy. The mechanism underlying lysophagy remains largely unknown; this study aimed to contribute to the understanding of this topic. A cell-based screening system was used to identify novel lysophagy modulators. Triamterene (6-phenylpteridine-2,4,7-triamine) was identified as one of the most potent lysophagy inducers from the screening process. We found that triamterene causes lysosomal rupture without affecting other cellular organelles and increases autophagy flux in HepG2 cells. Damaged lysosomes in triamterene-treated cells were removed by autophagy-mediated pathway, which was inhibited by depletion of the autophagy regulator, ATG5 or SQSTM1. In addition, treatment of triamterene decreased the integrity of lysosome and cell viability, which were rescued by removing the triamterene treatment in HepG2 cells. Hence, our data suggest that triamterene is a novel lysophagy inducer through the disruption of lysosomal integrity.
Assuntos
Autofagia/efeitos dos fármacos , Bloqueadores do Canal de Sódio Epitelial/farmacologia , Lisossomos/efeitos dos fármacos , Triantereno/farmacologia , Autofagia/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células HeLa , Células Hep G2 , Humanos , Lisossomos/metabolismoRESUMO
For development of green and sustainable energy, it is of importance to search highly efficient and low-cost electrocatalysts of oxygen reduction reaction (ORR) in energy conversion devices. Herein, CoFe alloyed nanocrystals embedded in N-doped bamboo-like carbon nanotubes (CoFe@NCNTs) were facilely synthetized by one-step co-pyrolysis with the mixture of triamterene, metal chlorides and graphitic carbon nitride (g-C3N4). The resultant CoFe@NCNTs exhibited excellent ORR activity with the positive shifts in the onset potential (Eonset = 0.97 V) and half-wave potential (E1/2 = 0.88 V), outperforming commercial Pt/C (Eonset = 0.96 V; E1/2 = 0.84 V). Compared to metal organic frameworks (MOFs)-based strategy for synthesis of low-cost carbon-based ORR catalysts, this method is simple and convenient, coupled by avoiding the complicated synthesis of MOFs and its ligands. This work provides a promising route to fabricate advanced transition-metal-based carbon catalysts in the researches correlated with energy conversion devices.
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we presented a case of drug-induced interstitial nephritis in a 43-year-old woman, having the history of renal calculi, as a result of sodium valproate and triamterene. Renal biopsy was used to confirm the diagnosis, however, due to poor prognosis along with discontinuation of drugs, she was treated with corticosteroids.
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SUMMARY: We report the case of a 76-year-old male with a remote history of papillary thyroid cancer who developed severe paroxysmal headaches in the setting of episodic hypertension. Brain imaging revealed multiple lesions, initially of inconclusive etiology, but suspicious for metastatic foci. A search for the primary malignancy revealed an adrenal tumor, and biochemical testing confirmed the diagnosis of a norepinephrine-secreting pheochromocytoma. Serial imaging demonstrated multiple cerebral infarctions of varying ages, evidence of vessel narrowing and irregularities in the anterior and posterior circulations, and hypoperfusion in watershed areas. An exhaustive work-up for other etiologies of stroke including thromboembolic causes or vasculitis was unremarkable. There was resolution of symptoms, absence of new infarctions, and improvement in vessel caliber after adequate alpha-adrenergic receptor blockade for the management of pheochromocytoma. This clinicoradiologic constellation of findings suggested that the etiology of the multiple infarctions was reversible cerebral vasoconstriction syndrome (RCVS). Pheochromocytoma remains a poorly recognized cause of RCVS. Unexplained multifocal cerebral infarctions in the setting of severe hypertension should prompt the consideration of a vasoactive tumor as the driver of cerebrovascular dysfunction. A missed or delayed diagnosis has the potential for serious neurologic morbidity for an otherwise treatable condition. LEARNING POINTS: The constellation of multifocal watershed cerebral infarctions of uncertain etiology in a patient with malignant hypertension should trigger the consideration of undiagnosed catecholamine secreting tumors, such as pheochromocytomas and paragangliomas. Reversible cerebral vasoconstriction syndrome is a serious but reversible cerebrovascular manifestation of pheochromocytomas that may lead to strokes (ischemic and hemorrhagic), seizures, and cerebral edema. Alpha-adrenergic receptor blockade can reverse cerebral vasoconstriction and prevent further cerebral ischemia and infarctions. Early diagnosis of catecholamine secreting tumors has the potential for reducing neurologic morbidity and mortality in patients presenting with cerebrovascular complications.
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Hypertension increases the risk of heart disease and stroke, is commonly known as a silent killer disease and considered as one of the key risk factor for premature death and disability over the world. Herein, we report for the first time a sensitive, costless and reproducible voltammetric method for individual determination of five antihypertensive drugs namely, propranolol (PRO), timolol (TIM), amlodipine (AML), amiloride (AMI) and triamterene (TRI) using differential pulse voltammetry at bare/unmodified screen-printed carbon electrodes (SPEs) in presence of sodium dodecyl sulfate (SDS). Each drug exhibits an electrochemical signal in aqueous media which is significantly enhanced in presence of optimized concentration of SDS due to accumulation of the protonated drug molecules and electrostatically interaction with negatively charged micellar structures. As a result, the spherical micellar orientation of SDS onto the graphitic surface of SPEs offered the analytically sensitive determination of the target drugs over a wide linear concentration range with nano-molar detection limits possible negating the need for any complicated surface modifications. Finally, the proposed voltammetric method was successfully utilized in the individual determination of the target antihypertensive drugs in pharmaceutical formulations and human urine samples.
Assuntos
Anti-Hipertensivos/análise , Técnicas Eletroquímicas , Impressão , Amilorida/análise , Anlodipino/análise , Avaliação Pré-Clínica de Medicamentos , Eletrodos , Humanos , Propranolol/análise , Timolol/análise , Triantereno/análiseRESUMO
The anticancer activity of triamterene on HCT116 and CT26 colon cancer cells lines was investigated. Furthermore, the mechanism of interaction between triamterene and calf thymus DNA (ct-DNA) and also human serum albumin (HSA) was conducted using spectroscopic and molecular docking techniques. In vitro cytotoxicity of triamterene against HCT116 and CT26 cells showed promising anticancer effects with IC50 values of 31.30 and 24.45 µM, respectively. Competitive studies of the triamterene with NR (neutral red) and MB (methylene blue) as intercalator probes showed that triamterene can be replaced by these probes. The viscosity data also confirmed that triamterene binds to calf-thymus DNA through intercalation binding mode. Binding properties of triamterene with HSA in the presence of warfarin and ibuprofen showed that triamterene competes with warfarin for the site I of human serum albumin (HSA). In addition, the binding modes of triamterene with DNA and HSA were verified by molecular docking technique. Abbreviations ct-DNA calf thymus DNA CV cyclic voltammetry DNA deoxyribonucleic acid DPV differential pulse voltammetry FBS fetal bovine serum HSA human serum albumin NR neutral red MB methylene blue MTT 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazoliumbromide Communicated by Ramaswamy H. Sarma.
Assuntos
DNA/química , Simulação de Acoplamento Molecular , Albumina Sérica Humana/química , Triantereno/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Ligação Competitiva , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA/genética , DNA/metabolismo , Células HCT116 , Humanos , Ibuprofeno/química , Ibuprofeno/metabolismo , Ibuprofeno/farmacologia , Camundongos , Ligação Proteica , Albumina Sérica Humana/metabolismo , Espectrometria de Fluorescência/métodos , Triantereno/química , Triantereno/metabolismo , Varfarina/química , Varfarina/metabolismo , Varfarina/farmacologiaRESUMO
Bilayer pseudo-stationary phase micellar liquid chromatography (MLC) was developed for simultaneous isocratic isolation of hydrochlorothiazide, as a basic-polar (hydrophilic) cardiovascular drug, as well as triamterene and losartan potassium, as acidic-nonpolar (hydrophobic) cardiovascular drugs. Utilizing a deep eutectic solvent (DES), as a novel green mobile phase additive in combination with acetonitrile (ACN) and acetic acid (ACA), drastically improved the chromatographic behavior of the drugs. Concentration of sodium dodecyl sulphate (SDS), as well as volume percentages of ACN, DES, and ACA were optimized by using a central composite design. The optimal composition of the mobile phase (0.12â¯molâ¯L-1 SDS, 5% ACN, 4% DES, and 2% ACA) was chosen through the desirability function. The chromatographic peaks of both hydrophilic and hydrophobic drugs, respectively, emerged at high and low retention time values in the shortest total analysis time of 20â¯min (at a flow rate of 2â¯mLâ¯min-1). Analytical characterization of the developed approach was investigated through Food and Drug Administration (FDA) guidelines. Applicability of the method was evaluated by analysing of human plasma samples which were directly injected into the system.