Scientia Pharmaceutica[JOURNAL]
Sun
200 papers
Six-Month Chronic Toxicity Study of Tamarind Pulp (Tamarindus indica L.) Water Extract.
Iskandar I, Setiawan F, Sasongko LD … +1 more , Adnyana IK
Sci Pharm · 2017 Mar · PMID 28282908 · Full text
Tamarind water extract has been shown to demonstrate an anti-obesity effect. In this research, long-term use of tamarind pulp water extract safety was evaluated. Tamarind pulp was extracted by reflux method, followed by...
Tamarind water extract has been shown to demonstrate an anti-obesity effect. In this research, long-term use of tamarind pulp water extract safety was evaluated. Tamarind pulp was extracted by reflux method, followed by freeze-drying to obtain dry extract. Wistar rats were divided into six groups, with 20 animals of each sex per group. The control group and satellite control group received carboxymethylcellulose sodium (CMC-Na) 0.5% 1 mL/100 g bw (body weight) per day. Treatment groups received tamarind pulp extract at doses of 75, 200, 1000, satellite 1000 mg/kg bw per day for six months. After six months, control groups and the treatment group were sacrificed. Satellite groups were sacrificed one month later. Relative organ weights, hematology and clinical biochemistry profiles were determined. After six months, there were no significant change in body weight, hematologic, and clinical biochemistry profiles of the tested group. Body weight of male rats in the satellite 1000 mg/kg bw group was significantly increased in week 30 compared to the satellite control group ( < 0.05). The relative spleen weight of female rats of the 200 mg/kg bw group was reduced ( < 0.05). The relative kidney weight of male rats in the 1000 mg/kg bw group was increased ( < 0.05). This study showed that tamarind pulp extract was generally safe and well tolerated at the tested dose.
Serum Cystatin C as a Biomarker in Diffuse Large B-Cell Lymphoma.
Hammouda NE, Salah El-Din MA, El-Shishtawy MM … +1 more , El-Gayar AM
Sci Pharm · 2017 Mar · PMID 28282874 · Full text
Elevated serum levels of cystatin C are found to be related to poor outcome and metastatic potential of some malignant disorders. To evaluate the clinical prominence of serum cystatin C in diffuse large B-cell lymphoma (...
Elevated serum levels of cystatin C are found to be related to poor outcome and metastatic potential of some malignant disorders. To evaluate the clinical prominence of serum cystatin C in diffuse large B-cell lymphoma (DLBCL), blood samples were obtained from 58 patients at the time of diagnosis and paired blood samples were obtained from 22 patients at the time of remission. Also, serum cystatin C level was measured in matched healthy controls. Serum cystatin C levels were significantly more elevated in DLBCL patients than in controls ( < 0.0001). Furthermore, paired-sample analysis revealed that pretreatment cystatin C levels were reduced significantly in patients who achieved remission after therapy ( = 0.016). High serum cystatin C levels were correlated with age over 60 years ( = 0.049), extra-nodal involvement ( = 0.005) and with high serum lactate dehydrogenase (LDH) ( < 0.013). Elevated serum cystatin C levels were associated with extra-nodal involvement and they were significantly reduced to normal range after the remission. However, Kaplan-Meier curves revealed no survival difference in the pretreatment serum cystatin C levels. Therefore, serum cystatin C may be a novel biomarker that reflects tumor burden in DLBCL but bears no prognostic significance regarding survival.
Anticancer Dose Adjustment for Patients with Renal and Hepatic Dysfunction: From Scientific Evidence to Clinical Application.
Hendrayana T, Wilmer A, Kurth V … +2 more , Schmidt-Wolf IG, Jaehde U
Sci Pharm · 2017 Feb · PMID 28264440 · Full text
Most anticancer agents exhibit a narrow therapeutic index, i.e., a small change in plasma concentrations can lead to a less efficacious treatment or an unacceptable degree of toxicity. This study aimed at providing healt...
Most anticancer agents exhibit a narrow therapeutic index, i.e., a small change in plasma concentrations can lead to a less efficacious treatment or an unacceptable degree of toxicity. This study aimed at providing health professionals with a feasible and time-saving tool to adapt the dose of anticancer agents for patients with renal or hepatic dysfunction. A guideline for anticancer agents was developed based on a literature search. An algorithm was generated to enhance the efficiency of the dose adaptation process. Finally, the dosing guideline was converted into an easy-to-use Excel tool. The concept was applied to a total of 105 adult patients at the Centre for Integrated Oncology, Bonn, Germany. In total, 392 recommendations for dose adaptation were made and 320 (81.6%) recommendations were responded to by the oncologists. 98.4% of the recommendations were accepted. The algorithm simplifies the decision and screening process for high-risk patients. Moreover, it provides the possibility to quickly decide which laboratory tests are required and whether a dose adjustment for a particular anticancer drug is needed. The Excel tool provides a recommended individual dose for patients with renal or hepatic dysfunction. The effectiveness of this strategy to reduce toxicity should be investigated in further studies before being adopted for routine use.
Antimutagenic Activity of Ethanol Extract of Rhaphidophora pinnata (L.f) Schott Leaves on Mice.
Masfria, Sumaiyah, Dalimunthe A
Sci Pharm · 2017 Feb · PMID 28218683 · Full text
is suggested to prevent or treat cancer of genetic mutations. In this study, antimutagenic activity of an ethanol extract of leaves was evaluated by using a bone marrow micronucleus assay on mice. Male mice (20-30 g) we...
is suggested to prevent or treat cancer of genetic mutations. In this study, antimutagenic activity of an ethanol extract of leaves was evaluated by using a bone marrow micronucleus assay on mice. Male mice (20-30 g) were treated for sevendays with an ethanol extract of leaves at a dose of 500, 750 and 1000 mg/kg/day/orally, prior to exposure to cyclophosphamide (i.p. 30 mg/kg), 24 h after the end of the treatment. Antimutagenic activity was determined by the decrease of micronuclei (MN). The results showed that a single administration of all variant doses of the extract had significantly decreased the micronucleus formation in bone marrow cell of mice as compared to the cyclophosphamide group. The ethanol extract of leaves had antimutagenic activity against cyclophosphamide-induced gene mutation.
A Validated Stability-Indicating HPLC Method for Simultaneous Determination of Amoxicillin and Enrofloxacin Combination in an Injectable Suspension.
Batrawi N, Wahdan S, Al-Rimawi F
Sci Pharm · 2017 Feb · PMID 28212319 · Full text
The combination of amoxicillin and enrofloxacin is a well-known mixture of veterinary drugs; it is used for the treatment of Gram-positive and Gram-negative bacteria. In the scientific literature, there is no high-perfor...
The combination of amoxicillin and enrofloxacin is a well-known mixture of veterinary drugs; it is used for the treatment of Gram-positive and Gram-negative bacteria. In the scientific literature, there is no high-performance liquid chromatography (HPLC)-UV method for the simultaneous determination of this combination. The objective of this work is to develop and validate an HPLC method for the determination of this combination. In this regard, a new, simple and efficient reversed-phase HPLC method for simultaneous qualitative and quantitative determination of amoxicillin and enrofloxacin, in an injectable preparation with a mixture of inactive excipients, has been developed and validated. The HPLC separation method was performed using a reversed-phase (RP)-C18e (250 mm × 4.0 mm, 5 μm) column at room temperature, with a gradient mobile phase of acetonitrile and phosphate buffer containing methanol at pH 5.0, a flow rate of 0.8 mL/min and ultraviolet detection at 267 nm. This method was validated in accordance with the Food and Drug Administration (FDA) and the International Conference on Harmonisation (ICH) guidelines and showed excellent linearity, accuracy, precision, specificity, robustness, ruggedness, 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.
Transmission Electron Microscopy of XDR Mycobacterium tuberculosis Isolates Grown on High Dose of Ofloxacin.
Arjomandzadegan M, Sadrnia M, Titov L … +4 more , Surkova L, Sarmadian H, Ghasemikhah R, Hosseiny H
Sci Pharm · 2017 Feb · PMID 28157163 · Full text
The aim of the study was to investigate behavior of resistant Mycobacterium tuberculosis (MTB) isolates under a high dose of ofloxacin and its morphological changes. 19 extensively drug resistant (XDR) clinical isolates o...
The aim of the study was to investigate behavior of resistant Mycobacterium tuberculosis (MTB) isolates under a high dose of ofloxacin and its morphological changes. 19 extensively drug resistant (XDR) clinical isolates of MTB were grown on Löwenstein-Jensen medium containing progressively increasing concentrations of ofloxacin (2, 4, 8, 16, 32 mg/L). Ultra-structure analyses of resistant isolates grown on ofloxacin were conducted by transmission electron microscopy (TEM). Fixation was carried out by 4% glutaraldehyde in 0.1 M sodium cacodylate buffer on 300 mesh carbon formvar copper grid. The samples were negatively stained with uranium acetate suspension. All19XDRMTBisolatesweregrownandformedcoloniessuccessfullyon2,4,8mg/L,sevenisolates on16mg/L,andfourisolateson32mg/Lofloxacin. Morphologicalchangesandunusualformswere detected in 8, 16 and 32 mg/L ofloxacin at 43%, 76.5% and 81% of cells, respectively. Swollen form (protoplast like), ghost-like cell, degraded forms, and in a few cases, detached cytoplasm from cell wall were clearly detected in high drug concentrations in comparison to control. Changes in morphology were increased with increasing ofloxacin concentrations (p < 0.05). Some XDR isolates could be successfully grown on high doses of ofloxacin (32 mg/L), but with changes in morphology. It was concluded that several magnitudes of the drug doses could not prevent growth of drug resistant forms.
Natural Products as New Treatment Options for Trichomoniasis: A Molecular Docking Investigation.
Setzer MS, Byler KG, Ogungbe IV … +1 more , Setzer WN
Sci Pharm · 2017 Jan · PMID 28134827 · Full text
Trichomoniasis, caused by the parasitic protozoan Trichomonas vaginalis, is the most common non-viral sexually-transmitted disease, and there can be severe complications from trichomoniasis. Antibiotic resistance in T. v...
Trichomoniasis, caused by the parasitic protozoan Trichomonas vaginalis, is the most common non-viral sexually-transmitted disease, and there can be severe complications from trichomoniasis. Antibiotic resistance in T. vaginalis is increasing, but there are currently no alternatives treatment options. There is a need to discover and develop new chemotherapeutic alternatives. Plant-derived natural products have long served as sources for new medicinal agents, as well as new leads for drug discovery and development. In this work, we have carried out an in silico screening of 952 antiprotozoal phytochemicals with specific protein drug targets of T. vaginalis. A total of 42 compounds showed remarkable docking properties to T. vaginalis methionine gamma-lyase (TvMGL) and to T. vaginalis purine nucleoside phosphorylase (TvPNP). The most promising ligands were polyphenolic compounds, and several of these showed docking properties superior to either co-crystallized ligands or synthetic enzyme inhibitors.
Chrysin Protects Rat Kidney from Paracetamol-Induced Oxidative Stress, Inflammation, Apoptosis, and Autophagy: A Multi-Biomarker Approach.
Kandemir FM, Kucukler S, Eldutar E … +2 more , Caglayan C, Gülçin İ
Sci Pharm · 2017 Jan · PMID 28134775 · Full text
Paracetamol (PC) is a safe analgesic and antipyretic drug at therapeutic doses, and it is widely used in clinics. However, at high doses, it can induce hepatotoxicity and nephrotoxicity. Chrysin (CR) is a natural flavono...
Paracetamol (PC) is a safe analgesic and antipyretic drug at therapeutic doses, and it is widely used in clinics. However, at high doses, it can induce hepatotoxicity and nephrotoxicity. Chrysin (CR) is a natural flavonoid that has biological activities that include being an antioxidant, an anti-inflammatory, and an anti-cancer agent. The main objective of this study was to investigate the efficacy of CR against PC-induced nephrotoxicity in rats. CR was given orally via feeding needle to male Sprague Dawley rats as a single daily dose of 25 or 50 mg/kg for six days. PC was administered orally via feeding needle as a single dose on the sixth day. PC caused significant glutathione depletion, lipid peroxidation, increased serum toxicity markers (serum urea and creatinine), and reductions in activities of antioxidant enzymes (superoxide dismutase - SOD, catalase - CAT, and glutathione peroxidase - GPx). The renal protective effect of CR was associated with decreasing the regulation of serum renal toxicity markers and increasing the regulation of antioxidant enzyme activities. Additionally, PC led to significant increases in the levels of inflammatory markers including tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-33 (IL-33). Furthermore, PC induced apoptotic tissue damage by increasing cysteine aspartate-specific protease-3 (caspase-3) activity and autophagic tissue damage by increasing the expression of light chain 3B (LC3B). CR therapy significantly decreased these values in rats. This study demonstrated that CR has antioxidant, anti-apoptotic, anti-inflammatory and anti-autophagic effects on PC-induced kidney toxicity in rats.
Quality Control of Traditional Cannabis Tinctures: Pattern, Markers, and Stability.
Peschel W
Sci Pharm · 2016 Apr · PMID 28117322 · Full text
Traditional tinctures of L. became obsolete before elucidation of the main cannabinoids and routine quality testing for medicines. In view of increasing medicinal use of cannabinoids and associated safety concerns, tinc...
Traditional tinctures of L. became obsolete before elucidation of the main cannabinoids and routine quality testing for medicines. In view of increasing medicinal use of cannabinoids and associated safety concerns, tinctures from a Δ9-tetrahydrocannabinol (THC)-type chemovar were studied. High-performance liquid chromatography with diode-array detection (HPLC/DAD) was used to determine THC, Δ9-tetrahydrocannabinolic acid A (THCA), cannabinol (CBN), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabigerol (CBG), cannabigerolic acid (CBGA), cannflavin A/B, and total phenolics. Derived group and ratio markers describe absolute and relative profiles when varying plant part (flos, folium), extraction solvent (EtOH percentage), storage conditions ('shelf' or 'fridge' up to 15 months), and pasteurization (2 h 70 °C, 20 min 80 °C). Tinctures from female flowering tops contained ten-fold more cannabinoids than tinctures from leaves; tinctures (80%-90% EtOH) contained ten-fold more cannabinoids than tinctures (40% EtOH). The analysis of CBGA + CBG, the main co-cannabinoids aside from THCA + THC, appears more relevant than CBDA + CBD. The decarboxylation of THCA to THC-the main change during storage of freshly prepared tinctures-is after 15 months in the 'fridge' comparable to 3 months on the 'shelf'. Minimally increased CBN totals did not correlate to diminished totals of THCA and THC (up to 15% after 3 months 'shelf', 45% after 15 months 'fridge'). Instead, total cannabinoids or acidic/neutral cannabinoid ratios are better stability markers. Moderate changes after pasteurization and partial losses below 10% for total cannabinoids after 9 months 'fridge' indicate possibilities for a reasonable shelf life. Yet storage and use of non-stabilized tinctures remain critical without authorized specification and stability data because a consistent cannabinoid content is not guaranteed.
Metabolite Profiles in Various Plant Organs of Justicia gendarussa Burm.f. and Its in Vitro Cultures.
Indrayoni P, Purwanti DI, Wongso S … +2 more , Prajogo BE, Indrayanto G
Sci Pharm · 2016 Apr · PMID 28117321 · Full text
Metabolite profiles of plant organs and their in vitro cultures of have been studied by using Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight-Mass Spectrometry (UPLC-Qtof-MS). Samples of leaves, stems,...
Metabolite profiles of plant organs and their in vitro cultures of have been studied by using Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight-Mass Spectrometry (UPLC-Qtof-MS). Samples of leaves, stems, roots, and shoot cultures showed similar patterns of metabolites, while samples of root cultures gave very different profiles. Concentrations of secondary metabolites in shoot cultures were relatively low compared to those in the leaves and roots of the plants. The results suggested that secondary metabolites in were biosynthetized in the leaves, then transported to the roots.
In Vivo Anticonvulsant Activity of Extracts and Protopine from the Fumaria schleicheri Herb.
Prokopenko Y, Tsyvunin V, Shtrygol' S … +1 more , Georgiyants V
Sci Pharm · 2015 Dec · PMID 28117320 · Full text
The present study aimed to investigate the role of several biologically active compounds from Soy.-Will. in anticonvulsant models. The flavonoid fraction, alkaloid fraction, individual alkaloid protopine, and polysaccha...
The present study aimed to investigate the role of several biologically active compounds from Soy.-Will. in anticonvulsant models. The flavonoid fraction, alkaloid fraction, individual alkaloid protopine, and polysaccharide-protein complex were isolated from the herb and studied along with dry extract in mice with pentylenetetrazole-induced seizures. According to empirical results, the expressed anticonvulsant effect of dry extract depends on the synergism of biologically active compounds in herbal medicine, although some individual substances (mostly protopine and the protein-polysaccharide fraction) have shown moderate anti-seizure activity.
Investigation of the Bioequivalence of Rosuvastatin 20 mg Tablets after a Single Oral Administration in Mediterranean Arabs Using a Validated LC-MS/MS Method.
Zaid AN, Al Ramahi R, Cortesi R … +4 more , Mousa A, Jaradat N, Ghazal N, Bustami R
Sci Pharm · 2016 Jun · PMID 28117319 · Full text
There is a wide inter-individual response to statin therapy including rosuvastatin calcium (RC), and it has been hypothesized that genetic differences may contribute to these variations. In fact, several studies have sho...
There is a wide inter-individual response to statin therapy including rosuvastatin calcium (RC), and it has been hypothesized that genetic differences may contribute to these variations. In fact, several studies have shown that pharmacokinetic (PK) parameters for RC are affected by race. The aim of this study is to demonstrate the interchangeability between two generic RC 20 mg film-coated tablets under fasting conditions among Mediterranean Arabs and to compare the pharmacokinetic results with Asian and Caucasian subjects from other studies. A single oral RC 20 mg dose, randomized, open-label, two-way crossover design study was conducted in 30 healthy Mediterranean Arab volunteers. Blood samples were collected prior to dosing and over a 72-h period. Concentrations in plasma were quantified using a validated liquid chromatography tandem mass spectrometry method. Twenty-six volunteers completed the study. Statistical comparison of the main PK parameters showed no significant difference between the generic and branded products. The point estimates (ratios of geometric mean %) were 107.73 (96.57-120.17), 103.61 (94.03-114.16), and 104.23 (94.84-114.54) for peak plasma concentration (C), Area Under the Curve (AUC), and AUC, respectively. The 90% confidence intervals were within the pre-defined limits of 80%-125% as specified by the Food and Drug Administration and European Medicines Agency for bioequivalence studies. Both formulations were well-tolerated and no serious adverse events were reported. The PK results (AUC and C) were close to those of the Caucasian subjects. This study showed that the test and reference products met the regulatory criteria for bioequivalence following a 20 mg oral dose of RC under fasting conditions. Both formulations also showed comparable safety results. The PK results of the test and reference in the study subjects fall within the acceptable interval of 80%-125% and they were very close to the results among Caucasians. These PK results may be useful in order to determine the suitable RC dose among Arab Mediterranean patients.
Synthesis, Structure, and Analgesic Properties of Halogen-Substituted 4-Hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxanilides.
Ukrainets IV, Petrushova LA, Shishkina SV … +3 more , Sidorenko LV, Sim G, Kryvanych OV
Sci Pharm · 2016 Jun · PMID 28117318 · Full text
As potential new analgesics, the corresponding 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxanilides have been obtained by amidation of ethyl 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylate with aniline and...
As potential new analgesics, the corresponding 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxanilides have been obtained by amidation of ethyl 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylate with aniline and its halogenated analogsin boiling dry xylene. The peculiarities of the mass and nuclear magnetic resonance (¹Н and С) spectra of the synthesized compounds are discussed. Using X-ray diffraction analysis, the ability of the compounds to form stable solvates with ,-dimethylformamide has been shown on the example of 4-bromo-substituted derivative. It should be further studied to be considered in their crystallization. According to the results of the pharmacological testing conducted on the model of the thermal tail-flick (tail immersion test) among halogen-substituted 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxanilides, substances which are considerably superior to meloxicam and piroxicam by their analgesic activity have been found. They are of interest for further profound studies.
Bioequivalence Study of Two Orodispersible Rizatriptan Formulations of 10 mg in Healthy Volunteers.
Cánovas M, Polonio F, Cabré F
Sci Pharm · 2016 Jun · PMID 28117317 · Full text
The aim of the study was to assess the bioequivalence and tolerability of two different oral formulations of rizatriptan. A bioequivalence study was carried out in 40 healthy volunteers according to an open label, random...
The aim of the study was to assess the bioequivalence and tolerability of two different oral formulations of rizatriptan. A bioequivalence study was carried out in 40 healthy volunteers according to an open label, randomized, two-period, two-sequence, crossover, single dose, and fasting conditions design. The test and reference formulations were administered in two treatment days, separated by a washout period of seven days. Plasma concentrations of rizatriptan were obtained by the LC/MS/MS (Liquid chromatography tandem-mass spectrometry) method. Log-transformed AUC (area under the plasma concentration-time curve from zero to the last measurable concentration) and C (maximum plasma concentration) values were tested for bioequivalence based on the ratios of the geometric means (test/reference). The t (time to reach maximum plasma concentration) was analysed nonparametrically. The 90% confidence intervals of the geometric mean values for the test/reference ratios for AUC and C were within the bioequivalence acceptance range of 80%-125%. According to the European Guideline, it may therefore be concluded that the test formulation of rizatriptan 10 mg orodispersible tablet is bioequivalent to the reference formulation (Maxalt Max 10 mg oral lyophilisate). The safety profile of both formulations was consistent with the summary of the product characteristics.
Anomalous Separation of Small Y-Chromosomal DNA Fragments on Microchip Electrophoresis.
Jabasini M, Ewis A, Sato Y … +2 more , Nakahori Y, Baba Y
Sci Pharm · 2016 May · PMID 28117316 · Full text
We investigated an anomalous DNA separation where two DNA fragments from the human Y-chromosome sY638 (64 bp) and sY592 (65 bp), with only one base pair difference, were separated. This result is abnormal since in a prev...
We investigated an anomalous DNA separation where two DNA fragments from the human Y-chromosome sY638 (64 bp) and sY592 (65 bp), with only one base pair difference, were separated. This result is abnormal since in a previous study, we found that 5 bp was the minimum difference between two DNA fragments that the microchip electrophoresis system can separate. The formation of a mini-loop in the structure of the DNA fragment of sY638 (64 bp) was strongly expected to be the reason. To investigate this, we synthesized three modified DNA fragments for sY638 (64 bp), and the modifications were in two expected locations for possible mini-loop formation. Later, the separation between sY592 (65 bp) and the three modified fragments of sY638 (64 bp) was not possible. Thus, we conclude that the formation of a mini-loop in the structure of the DNA is the reason behind this anomalous separation.
The Study of Structure-Analgesic Activity Relationships in a Series of 4-Hydroxy-2,2-dioxo-1H-2λ⁶,1-benzothiazine-3-carboxylic Acid Toluidides and Xylidides.
Ukrainets IV, Petrushova LA, Sidorenko LV … +2 more , Davidenko AA, Duchenko MA
Sci Pharm · 2016 Apr · PMID 28117315 · Full text
In continuing the search for new analgesics among derivatives of 2,1-benzothiazines, a series of corresponding toluidides and xylidides of 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylic acid has been synthesized...
In continuing the search for new analgesics among derivatives of 2,1-benzothiazines, a series of corresponding toluidides and xylidides of 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylic acid has been synthesized by the reaction of ethyl 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylate with equimolar amounts of mono- and dimethyl-substituted anilides in boiling dry xylene. Their structure has been confirmed by the data of elemental analysis, nuclear magnetic resonance (NMR) spectroscopy (¹Н and С), as well as mass spectrometry. All compounds obtained were subjected to pharmacological screening to identify their analgesic properties. Testing was carried out in male rats using the standard model of the thermal tail-flick (tail immersion test) in parallel and in comparison with the structurally related drugs meloxicam and piroxicam. Among the substances studied, highly active oral painkillers have been found; they exceed the analgesic effect of the reference drugs using the same dose. Interesting structural and biological regularities have been described; they will be useful in further research on creating promising new analgesics based on 4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxamides.
Benzotriazole-Mediated Synthesis and Antibacterial Activity of Novel N-Acylcephalexins.
Agha KA, Abo-Dya NE, Ibrahim TS … +2 more , Abdel-Aal EH, Hegazy WA
Sci Pharm · 2016 Apr · PMID 28117314 · Full text
Cephalexin () was acylated using -acylbenzotriazoles (-) derived from various carboxylic acids including aromatic, heterocyclic and -Pg-α-amino acid to afford -acylcephalexins in excellent yields (82%-96%). Antibacterial...
Cephalexin () was acylated using -acylbenzotriazoles (-) derived from various carboxylic acids including aromatic, heterocyclic and -Pg-α-amino acid to afford -acylcephalexins in excellent yields (82%-96%). Antibacterial screening of the novel cephalosporins revealed that all targets (-) retained the antibacterial activity of cephalexin against (ATCC 6538). -Nicotinylcephalexin () and -(3,4,5-trimethoxybenzoyl)cephalexin () exhibited a broader spectrum of antibacterial activity towards standard strains of (ATCC 6538), (ATCC 842), and (ATCC 10536) as well as a resistant strain of (ATCC 27853).
Estrogen Receptor Ligands: A Review (2013-2015).
Farzaneh S, Zarghi A
Sci Pharm · 2016 Apr · PMID 28117309 · Full text
Estrogen receptors (ERs) are a group of compounds named for their importance in both menstrual and estrous reproductive cycles. They are involved in the regulation of various processes ranging from tissue growth maintena...
Estrogen receptors (ERs) are a group of compounds named for their importance in both menstrual and estrous reproductive cycles. They are involved in the regulation of various processes ranging from tissue growth maintenance to reproduction. Their action is mediated through ER nuclear receptors. Two subtypes of the estrogen receptor, ERα and ERβ, exist and exhibit distinct cellular and tissue distribution patterns. In humans, both receptor subtypes are expressed in many cells and tissues, and they control key physiological functions in various organ systems. Estrogens attract great attention due to their wide applications in female reproductive functions and treatment of some estrogen-dependent cancers and osteoporosis. This paper provides a general review of ER ligands published in international journals patented between 2013 and 2015. The broad physiological profile of estrogens has attracted the attention of many researchers to develop new estrogen ligands as therapeutic molecules for various clinical purposes. After the discovery of the ERβ receptor, subtype-selective ligands could be used to elicit beneficial estrogen-like activities and reduce adverse side effects, based on the different distributions and relative levels of the two ER subtypes in different estrogen target tissues. Therefore, recent literature has focused on selective estrogen ligands as highly promising agents for the treatment of some types of cancer, as well as for cardiovascular, inflammatory, and neurodegenerative diseases. Estrogen receptors are nuclear transcription factors that are involved in the regulation of many complex physiological functions in humans. Selective estrogen ligands are highly promising targets for treatment of some types of cancer, as well as for cardiovascular, inflammatory and neurodegenerative diseases. Extensive structure-activity relationship studies of ER ligands based on small molecules indicate that many different structural scaffolds may provide high-affinity compounds, provided that some basic structural requirements are present.
New Synthesis, Structure and Analgesic Properties of Methyl 1-R-4-Methyl-2,2-Dioxo-1H-2λ⁶,1-Benzothiazine-3-Carboxylates.
Azotla-Cruz L, Lijanova IV, Ukrainets IV … +3 more , Likhanova NV, Olivares-Xometl O, Bereznyakova NL
Sci Pharm · 2017 Jan · PMID 28085092 · Full text
According to the principles of the methodology of bioisosteric replacements a series of methyl 1-R-4-methyl-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylates has been obtained as potential analgesics. In addition, a fundame...
According to the principles of the methodology of bioisosteric replacements a series of methyl 1-R-4-methyl-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylates has been obtained as potential analgesics. In addition, a fundamentally new strategy for the synthesis of compounds of this chemical class involving the introduction of -alkyl substituent at the final stage in 2,1-benzothiazine nucleus already formed has been proposed. Using nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry and X-ray diffraction analysis it has been proven that in the DMSO/K₂CO₃ system the reaction of methyl 4-methyl-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylate and alkyl halides leads to formation of -substituted derivatives with good yields regardless of the structure of the alkylating agent. The peculiarities of NMR (¹Н and С) spectra of the compounds synthesized, their mass spectrometric behavior and the spatial structure are discussed. In -benzyl derivative the ability to form a monosolvate with methanol has been found. According to the results of the pharmacological testing conducted on the model of the thermal tail-flick it has been determined that replacement of 4-ОН-group in methyl 1-R-4-hydroxy-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylates for the methyl group is actually bioisosteric since all methyl 1-R-4-methyl-2,2-dioxo-1-2λ⁶,1-benzothiazine-3-carboxylates synthesized demonstrated a statistically significant analgesic effect. The majority of the substances can inhibit the thermal pain response much more effective than piroxicam in the same dose. Under the same conditions as an analgesic the methyl-substituted analog exceeds not only piroxicam, but more active meloxicam as well. Therefore, it deserves in-depth biological studies on other experimental models.
Interaction between DNA and Drugs Having Protonable Basic Groups: Characterization through Affinity Constants, Drug Release Kinetics, and Conformational Changes.
Alarcón LP, Baena Y, Manzo RH
Sci Pharm · 2017 Jan · PMID 28054999 · Full text
This paper reports the in vitro characterization of the interaction between the phosphate groups of DNA and the protonated species of drugs with basic groups through the determination of the affinity constants, the rever...
This paper reports the in vitro characterization of the interaction between the phosphate groups of DNA and the protonated species of drugs with basic groups through the determination of the affinity constants, the reversibility of the interaction, and the effect on the secondary structure of the macromolecule. Affinity constants of the counterionic condensation DNA-drug were in the order of 10⁶. The negative electrokinetic potential of DNA decreased with the increase of the proportion of loading drugs. The drugs were slowly released from the DNA-drug complexes and had release kinetics consistent with the high degree of counterionic condensation. The circular dichroism profile of DNA was not modified by complexation with atenolol, lidocaine, or timolol, but was significantly altered by the more lipophilic drugs benzydamine and propranolol, revealing modifications in the secondary structure of the DNA. The in vitro characterization of such interactions provides a physicochemical basis that would contribute to identify the effects of this kind of drugs in cellular cultures, as well as side effects observed under their clinical use. Moreover, this methodology could also be projected to the fields of intracellular DNA transfection and the use of DNA as a carrier of active drugs.
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