Scientia Pharmaceutica[JOURNAL]
Sun
200 papers
Antibacterial Activity of Hen Egg White Lysozyme Denatured by Thermal and Chemical Treatments.
Vilcacundo R, Méndez P, Reyes W … +3 more , Romero H, Pinto A, Carrillo W
Sci Pharm · 2018 Oct · PMID 30380756 · Full text
The aim of this study was to increase the antibacterial spectrum of modified hen egg white lysozyme (HEWL) with thermal and chemical treatments against Gram-negative bacteria. The antibacterial activity of heat-denatured...
The aim of this study was to increase the antibacterial spectrum of modified hen egg white lysozyme (HEWL) with thermal and chemical treatments against Gram-negative bacteria. The antibacterial activity of heat-denatured HEWL and chemical denatured HEWL against Gram-negative and Gram-positive bacteria was evaluated in 15 h of incubation tests. HEWL was denatured by heating at pH 6.0 and pH 7.0 and chemical denaturing was carried out for 1.0, 1.5, 2.0, and 4.0 h with DL-Dithiothreitol (DTT). HEWL modified by thermal and chemical treatments was characterized using the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) electrophoresis method. Heat-denatured HEWL lytic activity against lessened with increasing temperature and time of incubation with the chemical agent (DTT). The loss of lytic activity in modified HEWL suggests that the mechanism of action of the antibacterial activity is not dependent on the lytic activity. Thermal and chemical treatments of HEWL enabled the production of oligoforms and increased antibacterial activity over a wider spectrum. Heat-denatured HEWL at pH 6.0 and chemically-denatured HEWL increased the HEWL antibacterial spectrum against Gram-negative bacteria ( ATCC 25922). HEWL at 120 °C and pH 6.0 (1.0 mg/mL) inhibited 78.20% of the growth of . HEWL/DTT treatment for 4.0 h (1.0 mg/mL) inhibited 68.75% of the growth . Heat-denatured HEWL at pH 6.0 and pH 7.0 and chemically-denatured HEWL (1.0, 1.5, 2.0, and 4.0 h with DTT) were active against Gram-positive bacteria ( CECT 4491T). Heat-denatured and chemical-denatured HEWL caused the death of the bacteria with the destruction of the cell wall. LIVE/DEAD assays of fluorescent dye stain of the membrane cell showed membrane perturbation of bacteria after incubation with modified HEWL. The cell wall destruction was viewed using electron microscopy. The results obtained in this study suggest that heat-denatured HEWL at pH 6.0 and chemical-denatured HEWL treatments increase the HEWL antibacterial activity against Gram-negative bacteria.
Isothiochromenothiazoles-A Class of Fused Thiazolidinone Derivatives with Established Anticancer Activity That Inhibits Growth of .
Kryshchyshyn A, Kaminskyy D, Nektegayev I … +2 more , Grellier P, Lesyk R
Sci Pharm · 2018 Oct · PMID 30347722 · Full text
Recently, thiazolidinone derivatives have been widely studied as antiparasitic agents. Previous investigations showed that fused 4-thiazolidinone derivatives (especially thiopyranothiazoles) retain pharmacological activi...
Recently, thiazolidinone derivatives have been widely studied as antiparasitic agents. Previous investigations showed that fused 4-thiazolidinone derivatives (especially thiopyranothiazoles) retain pharmacological activity of their synthetic precursors-simple 5-ene-4-thiazolidinones. A series of isothiochromeno[4a,4-][1,3] thiazoles was investigated in an in vitro assay towards bloodstream forms of . All compounds inhibited parasite growth at concentrations in the micromolar range. The established low acute toxicity of this class of compounds along with a good trypanocidal profile indicates that isothiochromenothiazole derivatives may be promising for designing new antitrypanosomal drugs.
NO-Donor Nitrosyl Iron Complex with 2-Aminophenolyl Ligand Induces Apoptosis and Inhibits NF-κB Function in HeLa Cells.
Stupina T, Balakina A, Kondrat'eva T … +3 more , Kozub G, Sanina N, Terent'ev A
Sci Pharm · 2018 Oct · PMID 30314357 · Full text
NO donating iron nitrosyl complex with 2-aminothiophenyl ligand ( complex) was studied for its ability to cause cell death and affect nuclear factor kappa B (NF-κB) signaling. The complex inhibited viability of HeLa cell...
NO donating iron nitrosyl complex with 2-aminothiophenyl ligand ( complex) was studied for its ability to cause cell death and affect nuclear factor kappa B (NF-κB) signaling. The complex inhibited viability of HeLa cells and induced cell death that was accompanied by loss of mitochondrial membrane potential and characteristic for apoptosis phosphatidylserine externalization. At IC50, caused decrease in nuclear content of NF-κB p65 polypeptide and mRNA expression of NF-κB target genes encoding interleukin-8 and anti-apoptotic protein BIRC3. mRNA levels of interleukin-6 and anti-apoptotic protein BIRC2 encoding genes were not affected. Our data demonstrate that NO donating iron nitrosyl complex can inhibit tumor cell viability and induce apoptosis that is preceded by impairment of NF-κB function and suppression of a subset of NF-κB target genes.
In Vivo Evaluation of ' Wound-Healing Activity.
Saqallah FG, Hamed WM, Talib WH
Sci Pharm · 2018 Oct · PMID 30301270 · Full text
Mediterranean-native perennial plant was scrutinized in this study for its antioxidant activity and its total phenolic content in order to test for the plant's wound-healing capability. The traditional uses of this plan...
Mediterranean-native perennial plant was scrutinized in this study for its antioxidant activity and its total phenolic content in order to test for the plant's wound-healing capability. The traditional uses of this plant to treat gum scurvy, various tumors, ulcers, and hemorrhoids were the main idea behind this study. Leaves and flowers of the were extracted by maceration. Pilot qualitative phytochemical tests were made to check the presence of various secondary metabolites. Quantitatively, the flowers' macerate indicated superlative results regarding antioxidant activity and total phenolic content. However, the in vivo wound-healing capability study was made using 30 Wistar strain albino rats. This innovative part of the study revealed that the healing power of the flowers' extract ointment (5% /) was superior compared to the leaves' extract (5% /) and the positive-control ointments (MEBO) (1.5% /) ( ≤ 0.001). This activity was assessed by visual examination, wound-length measurement, and estimation of hydroxyproline content. is a promising plant to be considered for wound healing. However, further testing (including histological examination and high-performance liquid chromatography (HPLC) analysis) is necessary to understand more about its mechanisms of action.
Potential Role of Microfibrillar-Associated Protein 4, Fibrotic Indices and Oxidative Stress in Hepatocellular Carcinoma.
Salama MM, Nomir MM, Fahmi MW … +2 more , El-Gayar AM, El-Shishtawy MM
Sci Pharm · 2018 Sep · PMID 30274364 · Full text
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. In an attempt to understand some potential mechanisms of persistence and oncogenicity of Hepatitis C virus (HCV)-related H...
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. In an attempt to understand some potential mechanisms of persistence and oncogenicity of Hepatitis C virus (HCV)-related HCC, microfibrillar-associated protein 4 (MFAP4), fibrotic indices and oxidative status biomarkers were assessed in the sera of 50 patients with HCV-associated HCC, 25 patients with HCV-related liver cirrhosis and 15 healthy individuals. Serum oxidized Coenzyme Q10 (CoQ10) and malondialdehyde showed significant elevation in HCC patients compared to the control group ( < 0.001), as well as cirrhotic patients ( < 0.05 and < 0.001, respectively), while serum glutathione content and superoxide dismutase activity were significantly decreased in HCC patients compared to the control group ( < 0.001). Serum MFAP4, aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the 4 factors (FIB-4) and Forns index showed significant increase in HCC patients compared to the control group ( < 0.001), while only APRI and FIB-4 were significantly different between HCC and cirrhotic patients ( < 0.05), with a sensitivity of 86% and 92%, respectively, at cut off ≥0.7 for APRI and ≥1.57 for FIB-4. Therefore, increasing oxidative stress and fibrosis might mediate HCV induced cirrhosis and HCC. APRI and FIB-4 may be used as a simple non-expensive formula for the screening of HCC rather than MFAP4.
Pharmacokinetic Enhancers (Boosters)-Escort for Drugs against Degrading Enzymes and Beyond.
Krauß J, Bracher F
Sci Pharm · 2018 Sep · PMID 30262788 · Full text
Pharmacokinetic enhancers (boosters) are compounds used in combination with a primary therapeutic agent (drug) and are not used for their direct effects on the disease but because they enhance or restore the activity of...
Pharmacokinetic enhancers (boosters) are compounds used in combination with a primary therapeutic agent (drug) and are not used for their direct effects on the disease but because they enhance or restore the activity of the primary agent. Hence, in certain cases, they represent an indispensable escort for enzyme-labile drugs. Pharmacokinetic enhancers can exert their activity on different ways. In the most common case, they inhibit enzymes such as human cytochrome P450 enzymes in the liver or other organs and, thereby, block or reduce undesired metabolism and inactivation of the primary drug. In this review, an overview will be given on the therapeutically most important classes of pharmacokinetic enhancers like β-lactamase inhibitors, inhibitors of CYP (cytochrome P450) enzymes in HIV therapy and hepatitis C, boosters for fluoropyrimidine-type anticancer agents, compounds utilized for enabling therapy of Parkinson's disease with levodopa, and others. Inhibitors of efflux pumps in both pathogenic bacteria and tumor cells will be addresses shortly.
Structure-Antibacterial Activity Relationships of -Substituted-(-/-Alaninyl) 1-1,2,3-Triazolylmethyl Oxazolidinones.
Phillips OA, Udo EE, D'silva RJ
Sci Pharm · 2018 Sep · PMID 30261667 · Full text
Bacterial resistance towards the existing class of antibacterial drugs continues to increase, posing a significant threat to the clinical usefulness of these drugs. These increasing and alarming rates of antibacterial re...
Bacterial resistance towards the existing class of antibacterial drugs continues to increase, posing a significant threat to the clinical usefulness of these drugs. These increasing and alarming rates of antibacterial resistance development and the decline in the number of new antibacterial drugs' approval continue to serve as a major impetus for research into the discovery and development of new antibacterial agents. We synthesized a series of -/-alaninyl substituted triazolyl oxazolidinone derivatives and evaluated their antibacterial activity against selected standard Gram-positive and Gram-negative bacterial strains. Overall, the compounds showed moderate to strong antibacterial activity. Compounds and (- and -alaninyl derivatives bearing the 3,5-dinitrobenzoyl substituent), (-alaninyl derivative bearing the 5-nitrofurancarbonyl group) and and (- and -alaninyl derivatives bearing the 5-nitrothiophene carbonyl moiety) demonstrated antibacterial activity (MIC: 2 µg/mL) against , , and standard bacterial strains. No significant differences were noticeable between the antibacterial activity of the - and -alaninyl derivatives as a result of the stereochemistry of the compounds.
Antifibrotic Activity and In Ovo Toxicity Study of Liver-Targeted Curcumin-Gold Nanoparticle.
Adlia A, Tomagola I, Damayanti S … +2 more , Mulya A, Rachmawati H
Sci Pharm · 2018 Sep · PMID 30248962 · Full text
Conjugation of curcumin and gold with green chemistry is an approach to improve the effectiveness of curcumin as anti-fibrosis. In this work, curcumin and gold were conjugated to deliver curcumin to the liver. Curcumin-g...
Conjugation of curcumin and gold with green chemistry is an approach to improve the effectiveness of curcumin as anti-fibrosis. In this work, curcumin and gold were conjugated to deliver curcumin to the liver. Curcumin-gold nanoparticles (cAuNPs) were prepared by varying curcumin pH and concentration. The successful of cAuNPs formation were identified by using UV-visible and FTIR spectrophotometers. The particle size and morphology were analyzed using particle size analyzer and cryo-TEM respectively. In vitro antioxidant assay was performed to determine the curcumin activity after conjugation. Physical and chemical stabilities of cAuNPs were studied for one month at 5 °C, 25 °C, and 40 °C. Furthermore, the cAuNPs activity to modulate early marker of fibrosis was tested on NIH/3T3 cells. The optimum condition for cAuNPs synthesis was by using 1.5 mM curcumin at pH 9.3. As compared to free curcumin, cAuNPs showed higher antioxidant activity and maintained the nanosize after stored for one month. In line with the antioxidant activity, cAuNPs 0.25⁻1 μg/mL reduced the collagen production by NIH/3T3 cells. More importantly, cAuNPs did not demonstrate any effect on the development of chicken embryo. Taken together, the attachment of gold to curcumin in the form of cAuNPs is promising for curcumin targeting to treat hepatic fibrosis.
In Vitro Antimicrobial Activity of Essential Oils from Sardinian Flora against (Formerly ) and Its Enhancement by Chitosan.
Juliano C, Marchetti M, Pisu ML … +1 more , Usai M
Sci Pharm · 2018 Sep · PMID 30217104 · Full text
The in vitro antibacterial activity of some essential oils from Sardinian flora, both alone and in combination with chitosan, was investigated against a strain of , a bacterium involved in pathogenesis of acne. The compo...
The in vitro antibacterial activity of some essential oils from Sardinian flora, both alone and in combination with chitosan, was investigated against a strain of , a bacterium involved in pathogenesis of acne. The composition of the essential oils was determined by gas chromatography and gas chromatography/mass spectrometry. The results of this investigation demonstrated that some of the oils examined, characterised by different chemical profiles, possessed some activity against . Interestingly, this antibacterial effect was enhanced by sub-inhibitory concentrations of chitosan. These observations suggest the potential application of this synergy in the development of innovative topical formulations useful in the management of acne.
Effect of Piperine on Skin Permeation of Curcumin from a Bacterially Derived Cellulose-Composite Double-Layer Membrane for Transdermal Curcumin Delivery.
Jantarat C, Sirathanarun P, Boonmee S … +2 more , Meechoosin W, Wangpittaya H
Sci Pharm · 2018 Sep · PMID 30216984 · Full text
Curcumin is a naturally occurring substance with various pharmacological activities. It has not been developed as a drug because of its low bioavailability due to its low solubility and absorption. Piperine is a natural...
Curcumin is a naturally occurring substance with various pharmacological activities. It has not been developed as a drug because of its low bioavailability due to its low solubility and absorption. Piperine is a natural enhancer that is popularly used to increase the absorption of curcumin in oral applications; however, it has not been applied for transdermal curcumin delivery. This study aims to develop a transdermal curcumin delivery system using piperine as a skin permeation enhancer in the form of composite double-layer membrane; the upper layer consisted of curcumin and the lower layer consisted of piperine. The amount of curcumin was fixed, but the amount of piperine varied at three levels from 1.96% to 7.41%. The composite membrane had moderate mechanical strength (15⁻22 MPa) with a good swelling degree (~435%). From an in vitro skin permeation study, piperine had the effect to increase the permeation of curcumin. The permeation rate was related to the amount of piperine. The composite membrane containing piperine at 7.41% could increase the permeation rate of curcumin by about 1.89 times compared with non-piperine contained membrane. Bacterially-derived cellulose containing curcumin and piperine may have the potential for transdermal curcumin delivery in order to improve curcumin's bioavailability.
Determination of Eudragit L100 in an Enteric-Coated Tablet Formulation Using Size-Exclusion Chromatography with Charged-Aerosol Detection.
Widjaja M, Gan J, Talpaneni JSR … +1 more , Tjandrawinata RR
Sci Pharm · 2018 Sep · PMID 30213090 · Full text
Eudragit L100 is a commonly used polymer in a coating layer of modified-release drug formulation to prevent drug release in the stomach. The amount of Eudragit L100 in the formula determines the dissolution profile of dr...
Eudragit L100 is a commonly used polymer in a coating layer of modified-release drug formulation to prevent drug release in the stomach. The amount of Eudragit L100 in the formula determines the dissolution profile of drug at its release medium. Hence, its quantification in reference product will facilitate the formulation of a bioequivalent drug product. Some analytical methods including size-exclusion chromatography (SEC) have been reported for characterization of Eudragit L100 either as single component or its conjugate with the enzyme, but none for its quantification in drug formulation. In this work, an SEC method with charged-aerosol detection (CAD) was developed for determination of Eudragit L100 in an enteric-coated tablet formulation using Waters Ultrahydrogel 1000 and Waters Ultrahydrogel 120 columns in series. The mobile phase was a mixture of 90:10 (/) 44.75 mM aqueous ammonium acetate buffer, pH 6.6 and acetonitrile pumped at a constant flow rate of 0.8 mL/min in isocratic mode. The method was validated for specificity, working range, limit of detection (LOD), limit of quantification (LOQ), accuracy and precision. The method was shown to be specific for Eudragit L100 against the diluent (mobile phase) and placebo of a coating layer for the tablet. A good correlation coefficient ( = 0.9997) of CAD response against Eudragit L100 concentration from 0.1⁻1.0 mg/mL was obtained using polynomial regression. LOD and LOQ concentrations were 0.0015 and 0.0040 mg/mL, respectively. The mean recovery of Eudragit L100 was in the range of 88.0⁻91.1% at three levels of working concentration: 50%, 100% and 150%. Six replicated preparations of samples showed good precision of the peak area with % relative standard deviation (RSD) 2.7. In conclusion, the method was suitable for quantification of Eudragit L100 in an enteric-coated tablet formulation.
Thai Fermented Foods as a Versatile Source of Bioactive Microorganisms-A Comprehensive Review.
Sivamaruthi BS, Kesika P, Chaiyasut C
Sci Pharm · 2018 Sep · PMID 30208667 · Full text
Fermented foods are known for several health benefits, and they are generally used among the Asian people. Microorganisms involved in the fermentation process are most responsible for the final quality of the food. Tradi...
Fermented foods are known for several health benefits, and they are generally used among the Asian people. Microorganisms involved in the fermentation process are most responsible for the final quality of the food. Traditional fermented (spontaneous fermentation) foods are a versatile source of bioactive molecules and bioactive microbes. Several reports are available regarding the isolation and characterization of potent strains from traditional fermented foods. A collection of information for easy literature analysis of bioactive microbes derived from Thai fermented food is not yet available. The current manuscript compiled information on bioactive (antimicrobial- and enzyme-producing probiotic) microbes isolated from naturally fermented Thai foods.
Potential Gastroprotective Activity of Rice Bran ( L.) Extracted by Ionic Liquid-Microwave-Assisted Extraction against Ethanol-Induced Acute Gastric Ulcers in Rat Model.
Trinovita E, Chany Saputri F, Mun'im A
Sci Pharm · 2018 Sep · PMID 30205486 · Full text
The presence of gamma-oryzanol in rice bran oil can be 10⁻20-fold higher than tocopherol and tocotrienol. Gamma-oryzanol has various pharmacological properties. The objective of this study was to evaluate the effectivene...
The presence of gamma-oryzanol in rice bran oil can be 10⁻20-fold higher than tocopherol and tocotrienol. Gamma-oryzanol has various pharmacological properties. The objective of this study was to evaluate the effectiveness of rice bran extract as a gastroprotective in reducing lesions in ethanol-induced acute gastric ulcer models in rat, using the ionic liquid-microwave-assisted extraction (IL-MAE) method. Rice bran extract was obtained using the IL-MAE method with ionic liquid (IL), 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM]BF₄ (concentration 0.7 M), and a ratio of solid/liquid of 15 g/mL, 15 min extraction time, and 10% microwave power. The rats were pretreated with rice bran extract at different doses (100, 200, and 400 mg/kg body weight; BW) for seven days and subsequently exposed to acute gastric lesions induced by 80% ethanol. Omeprazole (36 mg/kg BW) was used as a standard anti-ulcer drug. The ulcer index, gastric juice acidity, and mucus levels were measured to assess the degree of gastroprotection. The results showed that the oral administration of rice bran extract at a dose of 400 mg/kg BW significantly inhibited the development of ulcer formation by 66.75% and reduced gastric acid levels. Moreover, gamma oryzanol and omeprazole protected the gastric mucosa from ethanol-induced gastric lesions by increasing the level of gastric mucus. Rice bran extract is effective as a gastroprotective therapy sourced from natural ingredients in treating the incidence of gastric ulcers. Most likely, this is related to gamma oryzanol as a bioactive compound contained in rice bran ( L.).
The In Vitro Anti-Proliferative Interaction of Flavonoid Quercetin and Toxic Metal Cadmium in the 1321N1 Human Astrocytoma Cell Line.
Al-Hasawi NA, Amine SA, Novotny L
Sci Pharm · 2018 Sep · PMID 30201909 · Full text
Cadmium (Cd) is a toxic heavy metal occurring in the environment as an industrial pollutant. The systematic accumulation of Cd in the human body may lead to major health problems. Quercetin (QE) is a natural flavonoid wi...
Cadmium (Cd) is a toxic heavy metal occurring in the environment as an industrial pollutant. The systematic accumulation of Cd in the human body may lead to major health problems. Quercetin (QE) is a natural flavonoid widely distributed in plants and is a part of human diet. Many studies have demonstrated the multiple benefits of QE to humans in protecting cells of our bodies. The aim of this study was to investigate the effect of QE and Cd on the proliferation of astrocytoma 1321N1 cells. Results indicated that the simultaneous exposure of the cells to 200 µM QE and 16 μM Cd significantly reduced cell viability to 6.9 ± 1.6% with respect to vehicle-treated cells. Other experiments of QE pre-treatment followed by the exposure to Cd alone or with QE indicated significant but decreased ability of QE or Cd to reduce proliferation of the cells compared to their co-incubation. Our study suggested a synergetic anti-proliferative interaction of Cd and QE in malignantly transformed cells. This adds new information regarding the biological effects of QE.
Skin Penetration and Stability Enhancement of Seed Oil by 2-Hydroxypropyl-β-Cyclodextrin Inclusion Complex for Cosmeceutical Applications.
Ruksiriwanich W, Sirithunyalug J, Khantham C … +2 more , Leksomboon K, Jantrawut P
Sci Pharm · 2018 Sep · PMID 30200490 · Full text
This study aimed to encapsulate seed oil (CPSO) in 2-hydroxypropyl-β-cyclodextrin (HPβCD) cavities and investigate their biological activity, physicochemical stability, and skin penetration by vertical Franz diffusion c...
This study aimed to encapsulate seed oil (CPSO) in 2-hydroxypropyl-β-cyclodextrin (HPβCD) cavities and investigate their biological activity, physicochemical stability, and skin penetration by vertical Franz diffusion cells of the CPSO-HPβCD inclusion complex formulations. For biological activity studies-including 2,2-diphenyl-1-picryhydrazyl radical (DPPH) scavenging, metal ion chelating, and inhibition of lipid and tyrosinase inhibition activities-the CPSO-HPβCD inclusion complex exhibited lower inhibition activity than free CPSO. CPSO-HPβCD dispersion, serum, and gel formulations were prepared. All formulations containing the CPSO-HPβCD inclusion complex showed no significant changes in physical characteristics after three months' storage. The percentages of oleic acid remaining in all formulations were over 80% of the initial amount during a three-month stability study. For the skin-penetration study, compared to other formulations, the CPSO-HPβCD serum formulation exhibited the highest cumulative amount of oleic acid in the whole skin and flux through receptor fluid, after six hours, of 32.75 ± 1.25 µg/cm² and 1.02 ± 0.15 µg/cm²/h, respectively. The CPSO-HPβCD serum formulation also showed the proper viscosity. Hence, the CPSO-HPβCD inclusion complex will be beneficial for the further development of cosmeceutical products.
Cytotoxic Desulfated Saponin from Predicted to Have High Binding Affinity to the Oncogenic Kinase PAK1: A Combined In Vitro and In Silico Study.
Shahinozzaman M, Ishii T, Takano R … +3 more , Halim MA, Hossain MA, Tawata S
Sci Pharm · 2018 Aug · PMID 30200330 · Full text
Sea cucumbers have long been utilized in foods and Asiatic folk medicines for their nutritive and health benefits. Herein, three sea cucumber species were investigated and showed the highest cytotoxicity among these. Ne...
Sea cucumbers have long been utilized in foods and Asiatic folk medicines for their nutritive and health benefits. Herein, three sea cucumber species were investigated and showed the highest cytotoxicity among these. Next, a desulfated saponin, desulfated echinoside B (DEB), was purified from through bioassay-guided fractionation. LC-ESI-MS (Liquid chromatography-electrospray ionization mass spectrometry) analysis also showed to be a rich source of saponins. DEB showed cytotoxicity on cancer cells with IC values of 0.5⁻2.5 µM, and on brine shrimps with an IC value of 9.2 µM. In molecular docking studies, DEB was found to bind strongly with the catalytic domain of PAK1 (p21-activated kinase 1) and it showed binding energy of -8.2 kcal/mol compared to binding energy of -7.7 kcal/mol for frondoside A (FRA). Both of them bind to the novel allosteric site close to the ATP-binding cleft. Molecular dynamics (MD) simulation demonstrated that DEB can form a more stable complex with PAK1, remaining inside the allosteric binding pocket and forming the maximum number of hydrogen bonds with the surrounding residues. Moreover, important ligand binding residues were found to be less fluctuating in the DEB-PAK1 complex than in the FRA-PAK1 complex throughout MD simulation. Our experimental and computational studies showed that both DEB and FRA can act as natural allosteric PAK1 inhibitors and DEB appeared to be more promising than FRA.
Subchronic Toxicity Evaluation of Ethanol Extract of Lour. Leaf in Wistar Rats.
Harahap U, Yuandani, Marianne … +3 more , Agustya HM, Azizah DU, Alfiah SW
Sci Pharm · 2018 Sep · PMID 30181458 · Full text
extract has been investigated for its hepatoprotective activity. This current study was conducted to evaluate the subchronic toxic effect of Lour. leaf extract. The subchronic toxicity of ethanol extract of leaf was ev...
extract has been investigated for its hepatoprotective activity. This current study was conducted to evaluate the subchronic toxic effect of Lour. leaf extract. The subchronic toxicity of ethanol extract of leaf was evaluated by OECD (Organization for Economic Cooperation and Development) guidelines. The extract at doses of 125, 250, 500, 1000 mg/kg body weight (BW) were orally administered to the test animals for 90 days. Signs of toxicity and mortality were observed for 90 days and 118 days. The biochemistry, hematology, macropathology, relative organ weight and histopathology examination was also performed. The macroscopic and microscopic examinations of liver, lung, kidney, spleen and heart displayed normal color and texture after treatment, with ethanol extract leaf at doses of 125 and 250 mg/kg BW. The signs of toxicity, mortality, macroscopic and microscopic changes, as well as increasing biochemistry parameters were observed after treatment, with extract at the dose of 500 and 1000 mg/kg BW. However, the abnormal value of biochemistry parameters was returned to normal when the treatment was stopped. There was no effect on hematological parameters at all doses of extract. The ethanol extract leaf is untoxic for long-term use at dose 125 and 250 mg/kg BW. The toxic effect of at 500 and 1000 mg/kg BW was reversible.
The Study of the Structure-Diuretic Activity Relationship in a Series of New -(Arylalkyl)-6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1-pyrrolo-[3,2,1-]quinoline-5-carboxamides.
Ukrainets IV, Golik MY, Sidorenko LV … +4 more , Korniyenko VI, Grinevich LA, Sim G, Kryvanych OV
Sci Pharm · 2018 Aug · PMID 30158453 · Full text
In accordance with the principles of "me-too" technique, the preparative method for obtaining has been proposed, and the synthesis of a large series of new -(arylalkyl)-6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1-pyrrolo[3,2,...
In accordance with the principles of "me-too" technique, the preparative method for obtaining has been proposed, and the synthesis of a large series of new -(arylalkyl)-6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1-pyrrolo[3,2,1-]quinoline-5-carboxamides as structurally close analogs of tricyclic pyrrolo- and pyridoquinoline diuretics has been carried out. All target compounds were obtained with high yields and purity by amidation of ethyl ester of the corresponding 2-methyl-pyrroloquinoline-5-carboxylic acid with arylalkylamines in boiling ethanol. Their structure was confirmed by the data of elemental analysis, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry and polarimetry. Moreover, interpretations of their ¹H and C-NMR spectra, their mass spectrometric behavior, as well as peculiarities of the polarimetric studies were discussed. The effect of -(arylalkyl)-6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1-pyrrolo[3,2,1-]quinoline-5-carboxamides on the urinary function of the kidneys was studied in white rats by the standard method of oral administration in the dose of 10 mg/kg compared to hydrochlorothiazide. According to the results of the primary pharmacological screening, the structural and biological regularities that were unexpected, but interesting for further studies were revealed. Among the substances studied, the samples, which by their diuretic effect are not inferior and even superior to both the known hydrochlorothiazide and the lead structure of the pyrroloquinoline group, have been found. On this basis, it can be argued that the introduction of the methyl group made by us in position 2 of pyrrolo[3,2,1-]quinoline nucleus can be considered as a successful and promising implementation of the "me-too" cloning of tricyclic 4-hydroxyquinoline-2-one diuretics.
The Structure and Activity of Double-Nitroimidazoles. A Mini-Review.
Żwawiak J, Zaprutko L
Sci Pharm · 2018 Jul · PMID 30044443 · Full text
Many interesting applications have been found for nitroimidazoles as therapeutic agents. Among others, some of these compounds can radiosensitize hypoxic tumor cells. The introduction of a second nitroimidazole ring to t...
Many interesting applications have been found for nitroimidazoles as therapeutic agents. Among others, some of these compounds can radiosensitize hypoxic tumor cells. The introduction of a second nitroimidazole ring to the molecule can improve the level of its pharmacological effect. The aim of this article is to overview the literature concerning active compounds that contain two nitroimidazole moieties in their structures.
Inhibitory Effects and Killing Kinetics of Lactic Acid Rice Gel Against Pathogenic Bacteria Causing Bovine Mastitis.
Chotigarpa R, Na Lampang K, Pikulkaew S … +3 more , Okonogi S, Ajariyakhajorn K, Mektrirat R
Sci Pharm · 2018 Jul · PMID 30012999 · Full text
and are the major teat skin bacteria and lead to severe bovine mastitis. Teat antiseptic is an important tool for controlling intramammary infection. The antibacterial activity of lactic acid (LA) against one reference...
and are the major teat skin bacteria and lead to severe bovine mastitis. Teat antiseptic is an important tool for controlling intramammary infection. The antibacterial activity of lactic acid (LA) against one reference strain of ATCC 25923 and two field strains including and was investigated using the broth microdilution method. Its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were 0.5% for strains belonging to both species. An antiseptic preparation containing 5% LA with modified rice gel (LA-RG) was successfully prepared. Rheological behavior of LA-RG was found to be a pseudoplastic flow with thixotropy with viscosity of approximately 0.007 Pas. LA-RG exhibited a sufficient adhesive property in the rolling ball test with a length of 9.67 ± 0.04 cm. Killing kinetic studies of LA-RG showed that the killing rate of LA-RG was significantly faster than that of LA. After 32 min of exposure to LA-RG, approximately 86% and 60% of and were reduced, respectively. Abnormal bacterial cell surface after exposure to LA-RG was observed by scanning electron microscopy. It is concluded that LA-RG is a promising preparation as an alternative product for preventing mastitis in dairy cattle.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe