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OBJECTIVES: Plants were used as medicines thousands of years ago. Conventional medicine use is increasing and many of the currently used drugs are extracted from herbal sources. In Palestinian traditional medicine, the Alhagi mannifera plant is used for the treatment of cancer. Our study aimed to extract this plant using five solvent fractions, identifying their chemical compositions, and evaluating their antimicrobial and cytotoxic effects. METHODS: The successive technique was used to extract five solvent fractions of A. mannifera. While the spectral analysis was used to characterize quantitatively and qualitatively the chemical components of these extracts. The antimicrobial activity of plant extracts was evaluated against seven microbial strains using a broth micro-dilution assay. The cytotoxic activity was assessed using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay against cervical cancer cell line (HeLa). RESULTS: A total of 165 compounds were identified in A. mannifera different extracts. In the petroleum ether extract were found a total of 55 compounds. The major compounds were 2,5-cyclooctadien-1-ol (9.42%), 3-chloropropionic acid, heptyl ester (9.42%), carbonic acid, ethyl nonyl ester (9.42%) and chloroacetic acid. In methylene chloride extract a total of 11 compounds were found, and the major compounds were m-ainobenzenesulfonyl fluoride (14.35%), dodecane,2,6,10-trimethyl- (14.35%) and propanoic acid,2,2-dimethyl-,2-ethylexyl ester (14.35%). In chloroform extract, a total of 23 compounds were found. The major compounds were 5-ethyl-1-nonene (21.28%), and decanedioic acid, bis(2-ethylhexyl) ester (21.28%). In acetone extract were found a total of 47 compounds and the major compound was phenol,2,4-bis(1,1-dimethylethyl)- (5.22%). In methanol extract a total of 29 compounds were found and the major compounds were 3-o-methyl-d-glucose (10.79%), myo-inositol, 2-c-methyl- (10.79%), myo-inositol, 4-c-methyl- (10.79%), and scyllo-inositol,1C-methyl- (10.79%). All extracts showed antimicrobial activity. However, the petroleum ether extract showed the most potent antimicrobial effect against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, MRSA, and Candida albicans with minimal inhibitory concentration (MIC) values of 1.25, 1.25, 6.25, 0.325, 6.25, and 1.56 µg/mL, respectively. De facto, chloroform extract followed by ether extract displayed potential cytotoxic activity with IC50 values of 0.2 and 1.2 mg/mL, respectively. CONCLUSIONS: A. mannifera was found to contain a variety of phytochemicals and its chloroform extract showed a potent cytotoxic effect on HeLa cancer cells. In addition, petroleum ether showed potent antimicrobial agents and these extracts look promising as drug candidates. Further in vivo investigations should be conducted to provide the basis for developing new cancer and microbial infections treatments.
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Antiinfecciosos , Inositol , ÉsteresRESUMEN
BACKGROUND: Discovering and screening for potential anti-obesity, anti-diabetic, anticancer, and antioxidant treatments from natural products still in recent times the main goal for many pharmaceutical scientists. The present investigation aimed to evaluate the chemical constituents of Ephedra alata fruits various extracts and to assess their antioxidant, antiobesity, antidiabetic, and cytotoxic effects. RESULT: In this work, high content of flavonoids and phenols were observed in the methanol fraction of E. alata fruits, which reached 98.95 mg of RUE/g and 33.22 mg of GAE/g, respectively. The methanol fraction has significant inhibitory activity against DPPH, α-amylase, α-glucosidase, and lipase with an IC50 value of 1.07, 9.43, 46.16, and 66.48 µg/mL. respectively. Also has anticancer activity against HeLa cancer cell line. While the acetone fraction has potent antioxidant activity with IC50 5 µg/mL. CONCLUSION: The DPPH and digestive enzymes assays results showed that the methanolic fraction of E. alata fruits has potent antioxidant, anti-diabetic, and anti-obesity activities, which can be an excellent candidate for biological and chemical analysis and can be further subjected for isolation of the therapeutically active compounds with anticancer potency.
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BACKGROUND: Aloysia citriodora Palau (AC) is commonly known as Lemon Verbena and has been utilized as a medicinal tea in folkloric medicine for the treatment of abdominal spasm, anxiety, and fever. The present investigation aimed to identify the chemical ingredients of AC essential oil (EO) collected from two different locations in Palestine and to assess their antioxidant, antimicrobial, cytotoxic, and cyclooxygenase (COX) inhibitory effects. METHODS: Gas chromatography/mass spectroscopy (GC/MS) technique was used to identify the chemical components of the hydro-distilled EO from both regions, while DPPH, MTS, and COX assays were utilized to estimate the antioxidant, cytotoxic, and COX inhibitory activities of the EOs, respectively. Moreover, a broth microdilution assay was used to assess antimicrobial potentials against seven microbial strains. RESULTS: The GC/MS technique revealed the presence of 17 compounds from the AC collected from the Umm al-Fahm region and 13 compounds from the sample from the Baqa al-Gharbiyye region, while α-citral was the major component of both EOs, representing 47.62 and 43.46%, respectively. The Baqa al-Gharbiyye AC EO exerted more potent antioxidant activity than the Umm al-Fahm EO, with IC50 values of 11.74 ± 0.18 and 35.48 ± 0.14 µg/mL, respectively, while the positive control Trolox had antioxidant IC50 values of 2.45 ± 0.01 µg/mL. Interestingly, both EOs inhibited more potential activity against Methicillin-Resistant Staphylococcus aureus (MRSA) and Proteus vulgaris than Ciprofloxacin and Ampicillin antibiotics and also showed more potent antifungal activity against Candida albicans than Fluconazole. Moreover, the Baqa al-Gharbiyye AC EO had a more potent cytotoxic effect than the Umm al-Fahm EO, with IC50 values of 84.5 ± 0.24 and 33.31 ± 0.01 µg/mL, respectively, compared with Doxorubicin, which had an IC50 dose of 22.01 ± 1.4 µg/mL. The EOs from Baqa al-Gharbiyye showed potent activity against both COX-1 and COX-2 enzymes, with IC50 of 52.93 ± 0.13 and 89.31 ± 0.21 µg/mL, respectively, while the EOs from the Umm al-Fahm region showed weaker activity against these enzymes, with IC50 of 349.99 ± 0.33 and 1326.37 ± 1.13 µg/mL, respectively. CONCLUSION: Both characterized EOs have a huge variety of chemical components. The Baqa al-Gharbiyye AC EO has more potent antioxidant and cytotoxic activities than the Umm al-Fahm EO, but both have potential antimicrobial activity against MRSA, P. vulgaris, and C. albicans. These results suggest the use of AC EOs as promising sources of active ingredients in the food, cosmetic, and pharmaceutical industries.
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Antiinfecciosos , Antioxidantes , Inhibidores de la Ciclooxigenasa , Aceites Volátiles , Verbenaceae/química , Antiinfecciosos/análisis , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antioxidantes/análisis , Antioxidantes/química , Antioxidantes/farmacología , Supervivencia Celular/efectos de los fármacos , Inhibidores de la Ciclooxigenasa/análisis , Inhibidores de la Ciclooxigenasa/química , Inhibidores de la Ciclooxigenasa/farmacología , Cromatografía de Gases y Espectrometría de Masas , Células HeLa , Humanos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Aceites Volátiles/análisis , Aceites Volátiles/química , Aceites Volátiles/farmacologíaRESUMEN
The rise of the emergence of microbial resistance of antibiotics, the dangerous side effects of nonsteroidal anti-inflammatory drugs, and noncompetent medications of Alzheimer's, Parkinson's, and other neurodegenerative diseases prompt scientists to search for phytochemicals that could be utilized in the remedy of lethal diseases. Glechoma curviflora (Boiss.) Kuntze (Nepeta curviflora) is a medicinal herb growing in the eastern parts of the Mediterranean Sea Basin and is widely consumed as a tea. The leaves of this plant have been traditionally used for the treatment of various infectious diseases. The current research was designed to identify the chemical composition of Glechoma curviflora (Boiss.) essential oil (EO) and to assess its antibacterial, antifungal, and cyclooxygenase inhibitory activities and the biophysical gating effect on AMPA receptors. Twenty phytochemicals were identified from G. curviflora leaves and flowers EO amounting to almost 100% of the total constituents using GC-MS technique, of which 1,6-dimethylspiro[4.5]decane (27.51%) 1, caryophyllene oxide (20.08%) 2, and ß-caryophyllene (18.28%) 3 were the main constituents. The biophysical properties' effect from the plant extract on various AMPA-type receptors expressed in Human Embryonic Kidney (HEK293) cells was assessed by exploiting the whole-cell patch-clamp technique. Microdilution assay was adopted for assessing the antimicrobial property against eight virulent microbial strains whilst the cyclooxygenase inhibition effect was accomplished utilizing COX inhibitory screening colorimetric assay G. curviflora EO displayed potent activity against P. aeruginosa (MIC = 1.25 µg/mL), S. sonnei (MIC = 3.12 µg/mL), and E. coli (MIC = 1.25 µg/mL), compared with ciprofloxacin (positive control) and potent antibacterial activity against S. aureus, MRSA, S. sonnei, E. coli, and P. aeruginosa compared to Ampicillin (2nd positive control). It also showed anti-Candida (MIC = 6.25 µg/mL) and antimold (MIC = 3.125 µg/mL) activities compared with fluconazole (antifungal positive control). Likewise, our results showed an inhibition and biophysical impact of G. curviflora on all AMPARs subunits.
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The use of green tea and herbal tea for weight loss is increasing worldwide owing to the rising rates of obesity. There are concerns about the safety and quality of these herbal products owing to their increased consumption worldwide. In this study, we evaluated randomly collected samples of green tea and herbal tea and tested them for heavy metal and microbial contamination. Eighteen samples of green tea or herbal tea of widely used brands in Palestine were tested for heavy metal and microbial contamination. The results showed that 7 of the samples had toxic heavy metals such as chromium (Cr) and lead (Pb), and their concentrations were above the allowable limits set by the World Health Organization (WHO). Moreover, 6 of the samples that were tested had microbial contamination with high total aerobic microbial count (TAMC) and total yeast and mold count (TYMC). This could be due to improper handling and storage conditions of these herbal products. This study is the first of its kind in Palestine, and its results are forewarning to all the responsible authorities, including the Ministry of Health (MoH), to take immediate corrective actions such as quality control testing, auditing, and registration of marketed tea products.
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BACKGROUND: Medicinal plants are widely used in many cultures, traditions, and civilizations worldwide. Plants with high contents of the valuable biological compounds can efficiently cure many diseases. This study is aimed at assessing, for the first time, the anti-α-amylase, antilipase, antimicrobial, and cytotoxic activities of Nonea obtusifolia (Willd.) DC. of five extracts from Palestine. METHODS: The antimicrobial activity was estimated using well diffusion method for N. obtusifolia plant of five extracts against eight ATCC (American Type Culture Collection) and clinical isolates. The cytotoxic effects for these extracts were evaluated against HeLa (cervical) carcinoma cells using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Moreover, the lipase and α-amylase inhibitory properties were determined using standard biomedical assays. RESULTS: The acetone extract of N. obtusifolia plant showed a more potent α-amylase inhibitory compared with acarbose with IC50 values of 25.7 ± 0.08 and 28.18 ± 1.22 µg/ml, respectively. Additionally, the acetone and methanol extracts revealed moderate antilipase activity compared to orlistat with IC50 values of 30.19 ± 0.11, 33.11 ± 0.13, and 12.3 ± 0.35 µg/ml, respectively. The methylene chloride extract was found to inhibit the growth of all the tested bacterial and fungal strains and also found to have potential cytotoxic effect against HeLa cancer cell line. CONCLUSION: This research work reports for the first time the biological activity of N. obtusifolia from Palestine, and the results were promising indicating that N. obtusifolia extracts contain valuable bioactive molecules that have a potential anti-α-amylase, antilipase, antibacterial, and antifungal cytotoxic potentials. Therefore, N. obtusifolia could have a medical significance in the future.
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Amilasas/antagonistas & inhibidores , Antiinfecciosos/farmacología , Boraginaceae/química , Lipasa/antagonistas & inhibidores , Extractos Vegetales/farmacología , Acetona/química , Animales , Antibacterianos/farmacología , Antioxidantes/farmacología , Difusión , Células HeLa , Humanos , Concentración 50 Inhibidora , Lipasa/química , Lípidos/química , Cloruro de Metileno/química , Pruebas de Sensibilidad Microbiana , Orlistat/farmacología , Páncreas/enzimología , Fitoquímicos/farmacología , Hojas de la Planta/química , Plantas Medicinales/química , Porcinos , alfa-Amilasas/químicaRESUMEN
Paracetamol with ibuprofen or with naproxen are frequently prescribed by doctors in combination. It was found that patients using a combination of NSAID like acetaminophen and ibuprofen experienced less pain. Patients are more compliant if these two drugs are combined in an ester form and given in one dosage form. The esterified prodrugs are hydrolyzed in humans to their active forms. In this study, two esters of paracetamol combined with ibuprofen and naproxen were synthesized as prodrugs. The physiochemical properties of these products were identified. Moreover, the bioactivities of these prodrugs were tested for its anti-inflammatory and anticoagulant activities. The results showed an improved COX inhibition and anticoagulant activity compared with their parent drugs. The synthesized drugs are expected to improve patient's compliance in terms of administration frequency and will have better pharmacokinetic properties with fewer side effects.
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Pellitory plant (Parietaria judaica (PJ)) is one of the most widely used Arabian traditional medicinal plants due to its ability to cure several infectious diseases and other illnesses. The current study is aimed at assessing the phytoconstituents, antilipase, antiamylase, antimicrobial, and cytotoxic characters of the Pellitory plant (Parietaria judaica (PJ)). Phytochemical screening and procyanidin detection were conducted according to the standard phytochemical procedures. Porcine pancreatic lipase and α-amylase inhibitory activities were carried out using p-nitrophenyl butyrate and dinitrosalicylic acid assays, respectively. In addition, antimicrobial activity was determined utilizing a microdilution assay against several bacterial and fungal strains. Besides, the cytotoxic effect against HeLa cell line was tested employing 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. The quantitative test results revealed that the methanol fraction of PJ contains 18.55 ± 0.55 mg of procyanidin and has a potential α-amylase inhibitory activity compared with the antidiabetic drug Acarbose with IC50 values of 15.84 ± 2.25 and 28.18 ± 1.22 µg/ml, respectively. Also, it has a potential antilipase activity compared to the commercial antiobesity drug, Orlistat, with IC50 values of 38.9 ± 0.29 and 12.3 ± 0.35 µg/ml, respectively. The acetone, hexane, and methanol fractions have broad-spectrum antibacterial activity against the screened bacterial strains, while the acetone fraction has shown anticandidal activity with a MIC value of 0.195 mg/ml. The PJ hexane and acetone fractions decreased HeLa cell viability significantly (p value < 0.0001) by approximately 90% at the concentration of 0.625 mg/ml. The revealed outcomes showed that the methanol fraction has strong α-amylase and lipase inhibitory characters. Besides, acetone, hexane, and methanol fractions have broad-spectrum antibacterial activity, while the acetone fraction revealed potent antifungal activity against Candida albicans. Moreover, at low concentrations, hexane and acetone fractions have potent cytotoxic and antiproliferative activity against HeLa cancer cells. Nevertheless, PJ acetone, hexane, and methanol fractions can serve as an effective source of natural products to develop new antiobesity, antidiabetic, antimicrobial, and anticancer agents.
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Antibacterianos/farmacología , Antifúngicos/farmacología , Parietaria/química , Fitoquímicos/farmacología , Animales , Biflavonoides/análisis , Calibración , Catequina/análisis , Muerte Celular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Células HeLa , Humanos , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Pruebas de Sensibilidad Microbiana , Proantocianidinas/análisis , Porcinos , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/metabolismoRESUMEN
[This corrects the article DOI: 10.1155/2017/1728414.].
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INTRODUCTION: In traditional medicine, many pharmacological activities have already been ascribed to the genus of Teucrium plant. These include antirheumatic antispasmodic, anthelmintic, diuretic, hypoglycemic, and anticancer effects. The recent investigation aimed to characterize and estimate the chemical composition, anti-inflammatory, antioxidant, and anticancer potentials of the essential oil isolated by the microwave-ultrasonic apparatus from Teucrium pruinosum leaves collected from Palestine. METHODS: The essential oil (EO) was analyzed by Gas Chromatography equipped with mass spectrometry (GC-MS), while its anticancer activity was evaluated against HeLa cervical adenocarcinoma cells. The ability of T. pruinosum EO to inhibit the conversion of Arachidonic Acid (AA) to PGH2 by ovine COX-1 and human recombinant COX-2 was determined using a COX inhibitor screening assay. In addition, the antioxidant activity of the EO was evaluated on the basis of the scavenging activity with a stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, while Trolox was used as a positive control. RESULTS: Forty-four molecules were identified in T. pruinosum EO, representing 100% of the total EO. Agarospirol was found to be the most abundant component (45.53%) followed by caryophyllene (19.35%). However, the cyclooxygenase inhibitor assay revealed that T. pruinosum has potential COX-1 and Cox-2 inhibitory activity with IC50 values of 0.25 µg/ml and 0.5 µg/ml, respectively. Moreover, the T. pruinosum EO showed moderate antioxidant capacity with an IC50 value of 16.98±0.84 µg/ml in comparison with the positive control Trolox, which has an antioxidant potential with an IC50 value of 2.09±0.17 µg/ml. In addition, 250, 125, 62.5, 31.25, 15.625, 7.67, and 3.84 mg/ml of T. pruinosum EO treatments inhibited mitochondrial activity (cell viability) significantly and extremely by 90-95%. CONCLUSION: The current study provided data that revealed that the T. pruinosum EO could be a suitable candidate for use as a novel anticancer, anti-inflammatory, and antioxidant medication. Further clinical trials would be required to ensure these effects and to allow the design of suitable pharmaceutical dosage forms from this natural oil.
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Antioxidantes/farmacología , Inhibidores de la Ciclooxigenasa/farmacología , Aceites Volátiles/química , Teucrium/química , Animales , Antiinflamatorios , Cromatografía de Gases y Espectrometría de Masas , Humanos , Aceites Volátiles/farmacología , OvinosRESUMEN
Rutin is available in some foods, fruits, and vegetables. It has various beneficial medical effects making it useful in the treatment of various diseases. Rutin is available in different oral dosage forms such as tablets or capsules, widely available in the market. Rutin and many herbal medicines lack quality control due to unavailability of analytical methods. In this study, we formulated rutin tablet and studied its stability using a simple developed analytical method. The dissolution profile of our formulated tablet was also inspected. The results showed that our developed method was linear (R2 = 0.999), precise (% RSD = 0.026), and accurate (% recovery = 98.55-103.34). The formulated rutin tablet was stable under accelerated conditions as well as room temperature for 150 days (% assay > 91.69). The dissolution profile over 45 minutes of our formulated tablet showed a better dissolution (26.5%) compared with the internationally marketed Rutin® tablet (18.5%). This study can serve as a guideline to companies that manufacture herbal products to improve their formulated herbs and apply validated analytical methods to check the quality of their product.
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Menthol is widely used as a fragrance and flavor in the food and cosmetic industries. It is also used in the medical and pharmaceutical fields for its various biological effects. Gas chromatography (GC) is considered to be a sensitive method for the analysis of menthol. GC chromatographic separation was developed using capillary column (VF-624) and a flame ionization detector (FID). The method was validated as per ICH guidelines for various parameters such as precision, linearity, accuracy, solution stability, robustness, limit of detection, and quantification. The tested validation parameters were found to be within acceptable limits. The method was successfully applied for the quantification of menthol in suppositories formulations. Quality control departments and official pharmacopeias can use our developed method in the analysis of menthol in pharmaceutical dosage formulation and raw material.
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Natural plants products are one of the famous and commonly utilized remedies used in fighting diseases. This study was conducted to evaluate antioxidant activity of plants commonly used in Palestine (Urtica urens, Rumex cyprius and Borago officinalis). Free radical scavenging activity method was evaluated by using 2,2-diphenyl-1-picryl-hydrazyl-hydrate. The result show that the overall antioxidant activity of Rumex cyprius was the highest among the plants, followed by Urtica urens, and Borago officinalis; respectively. The (IC(50)) values of the methanolic extracts were 29.70±0.60µg/ml, 5.07±0.49µg/ml, 39.92± 0.52 µg/ml for Urtica urens, Rumex cyprius and Borago officinalis respectively. The results of this study revealed that these edible plants have high antioxidant activity and therefore they can provide natural sources of antioxidants and can be useful in preventing various diseases including cancer. These exhibited properties propose that such plants extracts can possibly be used as natural preservatives in the food and pharmaceutical industries and further characterization of Rumex cyprius constituents is needed.
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Antioxidantes/química , Borago/química , Plantas Comestibles/química , Rumex/química , Urticaceae/química , Antioxidantes/farmacología , Compuestos de Bifenilo , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Israel , Picratos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/químicaRESUMEN
BACKGROUND: Montelukast (MT) is a leukotriene D4 antagonist. It is an effective and safe medicine for the prophylaxis and treatment of chronic asthma. It is also used to prevent acute exercise-induced bronchoconstriction and as a symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis. OBJECTIVE: The aim of this study was to evaluate the bioequivalence (BE) of two drug products: generic MT 5 mg chewable tablets versus the branded drug Singulair(®) pediatric 5 mg chewable tablets among Mediterranean volunteers. METHODS: An open-label, randomized two-period crossover BE design was conducted in 32 healthy male volunteers with a 9-day washout period between doses and under fasting conditions. The drug concentrations in plasma were quantified by using a newly developed and fully validated liquid chromatography tandem mass spectrometry method, and the pharmacokinetic parameters were calculated using a non-compartmental model. The ratio for generic/branded tablets using geometric least squares means was calculated for both the MT products. RESULTS: The relationship between concentration and peak area ratio was found to be linear within the range 6.098-365.855 ng/mL. The correlation coefficient (R (2)) was always greater than 0.99 during the course of the validation. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between the generic and branded products. The point estimates (ratios of geometric means) were 101.2%, 101.6%, and 98.11% for area under the curve (AUC)0âlast, AUC0âinf, and C max, respectively. The 90% confidence intervals were within the predefined limits of 80.00%-125.00% as specified by the US Food and Drug Administration and European Medicines Agency for BE studies. CONCLUSION: Broncast(®) pediatric chewable tablets (5 mg/tablet) are bioequivalent to Singulair(®) pediatric chewable tablets (5 mg/tablet), with a similar safety profile. This suggests that these two formulations can be considered interchangeable in clinical practice.
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Acetatos/administración & dosificación , Acetatos/farmacocinética , Cromatografía Liquida , Medicamentos Genéricos/administración & dosificación , Medicamentos Genéricos/farmacocinética , Antagonistas de Leucotrieno/administración & dosificación , Antagonistas de Leucotrieno/farmacocinética , Masticación , Quinolinas/administración & dosificación , Quinolinas/farmacocinética , Espectrometría de Masas en Tándem , Acetatos/sangre , Acetatos/química , Administración Oral , Adolescente , Adulto , Área Bajo la Curva , Química Farmacéutica , Estudios Cruzados , Ciclopropanos , Medicamentos Genéricos/química , Voluntarios Sanos , Humanos , Antagonistas de Leucotrieno/sangre , Antagonistas de Leucotrieno/química , Modelos Lineales , Masculino , Persona de Mediana Edad , Modelos Biológicos , Quinolinas/sangre , Quinolinas/química , Reproducibilidad de los Resultados , Sulfuros , Comprimidos , Equivalencia Terapéutica , Adulto JovenRESUMEN
Lincomycin and spectinomycin combination therapy is widely used in veterinary medicine for the treatment of gastrointestinal and respiratory infections caused by lincomycin- and spectinomycin-sensitive microorganisms. A simple, reverse phase HPLC method for the analysis of samples of an injectable lincomycin and spectinomycin preparation containing a mixture of inactive excipients has been developed. The HPLC was carried out using the RP-C(18) (250 mm × 4.0 mm, 5 µm) column, with the gradient mobile phase consisting of an acetonitrile and phosphate buffer at pH 6; the flow rate of 1 mL/min and ultraviolet detection at 220 nm. This method was validated in accordance with both FDA and ICH guidelines and showed good linearity, accuracy, precision, selectivity, and system suitability results within the acceptance criteria. A stability-indicating study was also carried out and indicated that this method can also be used for purity and degradation evaluation of these formulations.
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S-Trityl L-cysteine (STLC) is an inhibitor of the mitotic kinesin Eg5 with potential as an antimitotic chemotherapeutic agent. We previously reported the crystal structure of the ligand-protein complex, and now for the first time, have quantified the interactions using a molecular dynamics based approach. Based on these data, we have explored the SAR of the trityl head group using the methylene shuffle strategy to expand the occupation of one of the hydrophobic pockets. The most potent compounds exhibit strong (<100 nM) inhibition of Eg5 in the basal ATPase assay and inhibit growth in a variety of tumour-derived cell lines.