The main effects and application of glucocorticosteroids in clinical practice. A multidisciplinary approach

Glucocorticosteroids are hormones produced by the adrenal cortex. The term also refers to semi-synthetic drugs such as prednisolone, dexamethasone and other drugs that are derivatives of hydrocortisone, the most active natural glucocorticosteroid. Cortisone is a biologically inactive compound that is converted to hydrocortisone in the liver. Both natural glucocorticosteroids have mineralocorticoid activity, but weaker than genuine mineralocorticoids.

Determination Of Trometamol Content In Gadobutrol Solution For Intravenous Administration, 1 mmol / mL Using RP-LC With Refractive Index Detector

Background: Extremely responsive technique designed for the willpower of trometamol for instance tris(hydroxymethyl)aminomethane in gadobutrol by RP-LC technique. Quantification of trometamol content in gadobutrol samples by HPLC with refractive index detector (RID). Trometamol was UV inactive compound.Methods: Trometamol was determined by RP-LC method using Inertsil NH2 (250x4.6mm, 5µm) column as motionless segment. Column temperature maintained 30°C, inoculation quantity 10µL, flow velocity was 0.3 ml/min, sample cooler temperature 25°C. The mixture of phosphate buffer and cyanomethane in the ratio of 990:10 (volume/volume) was utilized as movable segment. The retention time of trometamol determined 10.95 minutes respectively. The acceptance limit of the trometamol content is 0.9%-1.5%.ConclusionThe proposed RP-LC technique that can determination of trometamol content in gadobutrol solution intravenous administration contain expanded as well as authenticated as per ICH guidelines. The efficiency of the technique was ensure by the specificity, exactitude and accuracy. Hence, the technique well suit for their intended purposes and can be productively useful for the release testing of gadobutrol injection keen on the souk.

Thiosemicarbazones as Potent Anticancer Agents and their Modes of Action

: Thiosemicarbazones (TSCs) are a class of Schiff bases usually obtained by the condensation of thiosemicarbazide with a suitable aldehyde or ketone. TSCs have been the focus of chemists and biologists due to their wide range of pharmacological effects. One of the promising areas in which these excellent metal chelators are being developed is their use against cancer. TSCs have a wide clinical antitumor spectrum with efficacy in various tumor types such as leukemia, pancreatic cancer, breast cancer, non-small cell lung cancer, cervical cancer, prostate cancer and bladder cancer. To obtain better activity, different series of TSCs have been developed by modifying the heteroaromatic system in their molecules. These compounds possessed significant antineoplastic activity when the carbonyl attachment of the side chain was located at a position α to the ring nitrogen atom, whereas attachment of the side chain β or γ to the heterocyclic N atom resulted in inactive antitumor agents. In addition, replacement of the heterocyclic ring N with C also resulted in a biologically inactive compound suggesting that a conjugated N,N,S-tridentate donor set is essential for the biological activities of thiosemicarbazones. Several possible mechanisms have been implemented for the anticancer activity of thiosemicarbazones.

Controlling phase transformation during milling in the pre-formulation of Active pharmaceutical Ingredients

A high percentage of active pharmaceutical ingredient are available in the insoluble crystalline phase. During pharmaceutical processing such as milling there are many issues can be initiated due to the transformation of this crystalline materials. Some trans-formation might be positively solving the active pharmaceutical ingredients (APIs) problems such as solubility and dissolution rate while others might negatively affect these factors which render the APIs into inactive compound. Therefore, during the pre-formulation study, all of these issues must be resolved to ensure drug stability and hence its bioavailability. This review will shed the light on the most popular transformations that happened, factors affecting them, and the characterization methods used for the detection of phase formed. The studying of these factors, will help to avoid them in future

Synthesis of mono-functionalized S-diazocines via intramolecular Baeyer–Mills reactions

Herein we report a reliable method to synthesize mono-functionalized S-diazocines in reproducible yields via intramolecular Baeyer–Mills reactions. Diazocines exhibit excellent photoswitchable properties. As opposed to azobenzenes they are more stable in their cis configuration. Particularly in photopharmacology mono-functionalized diazocines should be potentially useful and superior to the frequently used azobenzenes because the sterically more demanding cis configuration should be inactive, and the slender trans configuration should fit in a tight binding pocket of a receptor. Hence, it should be possible to administer the stabile inactive compound and switch it on at the site of illness with visible light. To date only a limited number of diazocine derivatives have been published of which most are symmetrically functionalized. Using the Baeyer–Mills reaction for the synthesis of diazocines opens a novel and convenient access to unsymmetrically substituted diazocines.

Sexual Behavior in Males From a Neuroendocrine Perspective

It is well established that testosterone from testicular origin plays a critical role in the activation of male sexual behavior in most, if not all, vertebrate species. These effects take place to a large extent in the preoptic area although other brain sites are obviously also implicated. In its target areas, testosterone is actively metabolized either into estrogenic and androgenic steroids that have specific behavioral effects or into inactive metabolites. These transformations either amplify the behavioral activity of testosterone or, alternatively, metabolism to an inactive compound dissipates any biological effect. Androgens and estrogens then bind to nuclear receptors that modulate the transcription of specific genes. This process is controlled by a variety of co-activators and co-repressors that, respectively, enhance or inhibit these transcriptional processes. In addition, recent work has shown that the production of estrogens by brain aromatase can be modulated within minutes by changes in neural activity and that these rapid changes in neuroestrogen production impact sexual behavior, in particular sexual motivation within the same time frame. Estrogens thus affect specific aspects of male sexual behavior in two different time frames via two types of mechanisms that are completely different. Multiple questions remain open concerning the cellular brain mechanisms that mediate testosterone action on male sexual behavior.

THE INFLUENCE OF METISEVIT AND METIFEN ON THE INTENSITY OF LIPID PER OXIDATION IN THE BLOOD OF BULLS ON NITRATE LOAD

The level of primary and secondary lipid per oxidation products were investigated: diene conjugates and malondialdehyde in conditions of nitrate loading. It was established that at bulls feeding with sodium nitrite at a dose of 0.2 hNO3ˉ/kg of body weight, the level of diene conjugates and malondialdehyde in their was increased during the entire the experiment. On the 30thday of the experiment the level of diene conjugates in blood of bull, which were conducted with nitrate load was 7.44 ± 0.15 mmol/l, and the level of malondialdehyde – 0.305 ± 0.014 mmol/l.Under conditions of nitrate load , young cattle was used a new integrated drug «Metisevit», which consists of sodium selenite, vitamin E and metifen. It was found the stimulating effect of metifen and metisevit on antioxidant system of the body of young cattle. Depressing effect of metifen and metisevit on the processes and lipid per oxidation in the blood of bulls under conditions of chronic nitrate–nitrite toxicity. Metifen and metisevit interact with radicals of fatty acids and delay the development of a chain reaction of oxidative stress, reduce the oxidation of phospholipids and form a biologically inactive compound with products of per oxidation of fats. Obtained results of the research indicate antioxidant drugs «Metisevit» and «Metifen» in the application of their young cattle.The mentioned changes are occurring through the comprehensive action of the drug components «Medisvit», that leads to the normalization of metabolic processes and free radical in the body of bulls. Obtained results of the research indicate the antioxidant action of the drugs «Metisevit» and «Metifen» in the application of their young cattle and the reasonableness of their administration to improve the antioxidant status of the organism according to nitrate loading.

Selective Inhibition of EZH2 and EZH1 Enzymatic Activity By a Small Molecule Suppresses MLL rearrangement-Induced Leukemia

Enhancer of Zeste Homolog-2 (EZH2) and Related EZH1 Control Gene Expression and Promote Oncogenesis Via Methylating Histone H3 Lysine 27 (H3K27). These Methyltransferases Are Proposed to be Therapeutic Targets Due to Their Hyperactive Mutations and Overexpression Found in Cancer Including Various Hematological Malignancies. Here, We Characterized a Set of Small Molecules That Allow Pharmacological Manipulation of EZH2 and EZH1, Which Include UNC1999, a Highly Selective Inhibitor of Both Enzymes, and Its Di-Methylated Analog UNC2400, an Inactive Compound Useful to Assess Off-Target Effects. We Show That UNC1999 Suppresses H3K27 Tri- and Di-Methylation Globally and Inhibits Growth of MLL-Rearranged Leukemia Lines. Mechanistically, UNC1999 Preferentially Affects the Regulatory Elements Such As Enhancers and Distal Promoters, Leading to De-Repression of Many Known Polycomb Target Genes. Gene De-Repression Correlates with Decrease in H3K27me3 and Concurrent Gain in H3K27 Acetylation. UNC2400 Does Not Induce These Effects, Demonstrating UNC1999’s on-Target Inhibition. Oral Administration of UNC1999 Significantly Prolongs the Survival of a Well-Defined Murine Leukemia Model Generated By MLL-AF9. Thus, Our Studies Provide Detailed Profiling of a Set of Compounds for Studying EZH2 and EZH1 in Cancer and Establish Specific Inhibition of EZH2 and EZH1 Enzymatic Activities By Small Molecules As a Promising Therapeutics for MLL-Rearranged Leukemia. Disclosures No relevant conflicts of interest to declare.

SYNTHESIS OF 4-(4-METHOXY-PHENYL)-3-BUTENE-2-ON AND THE ACTIVITY TEST AS A FRUIT FLIES ATRACTANT

4-(4-methoxyphenyl)-3-buten-2-on has been synthesized from p-anisaldehyde and acetone via aldol condensation. The reaction was performed at room temperature under basic condition for 12 hours to give brown solid of product (m.p 64-65 oC) in 66.19 % yield. p-anisaldehyde itself was produced from oxidation of anetol major component of anise oil by the use of potassium permanganate as a oxidator. The structure of the products was analyzed by FTIR, 1H NMR and GC-MS. Activity test of 4-(4-methoxyphenyl)-3-buten-2-on as an attractant was carried out in Sleman with methyl eugenol as a reference. The result showed that 4-(4-methoxyphenyl)-3-buten-2-on was inactive compound as a fruit flies attractant and some of fruit flies, i.e. Bactrocera papayae, B. carambolae, B. umbrosa and B. abdolonginqua was found on the test area. Keywords: 4-(4-metoxy-phenyl)-3-butene-2-on, Bactrocera spp., attractant