Knowledge of Hormonal Contraception Among Young Women in Poland

Introduction. Hormonal contraception could activate wide range of biological effects in women body and what’s important these pharmaceuticals are often used for long time. The aim of this study was to examine the level of knowledge among young women studying on the universities of Bydgoszcz (Poland) about the health effects of hormonal contraception. Materials and Methods. 172 women aged from 18 to over 25 years (the majority of respondents were in the age 21-24 years) were assessed with original anonymous questionnaire. Results. The state of knowledge of young women concerning negative aspects of using contraception differs depending on field of study. The awareness of women using contraception was higher than women which didn’t use hormonal contraception. Conclusion. General state of knowledge of studied women concerning using hormonal contraception was not satisfactory. Especially alarming is ignorance of health threads connected with using hormonal contraception among women using this method of contraception

Pyridoxine-Dependent Epilepsy and Antiquitin Deficiency Resulting in Neonatal-Onset Refractory Seizures

Pyridoxine-dependent epilepsy (PDE) is an autosomal recessive neurometabolic disorder due to a deficiency of α-aminoadipic semialdehyde dehydrogenase (mutation in ALDH7A1 gene), more commonly known as antiquitin (ATQ). ATQ is one of the enzymes involved in lysine oxidation; thus, its deficiency leads to the accumulation of toxic metabolites in body fluids. PDE is characterized by persistent, recurrent neonatal seizures that cannot be well controlled by antiepileptic drugs but are responsive clinically and electrographically to daily pyridoxine (vitamin B6) supplementation. Although the phenotypic spectrum distinguishes between typical and atypical, pyridoxine-dependent is true for each. Diagnosis may pose a challenge mainly due to the rarity of the disorder and the fact that seizures may not occur until childhood or even late adolescence. Moreover, patients may not demonstrate an obvious clinical or electroencephalography response to the initial dose of pyridoxine. Effective treatment requires lifelong pharmacologic supplements of pyridoxine, and dietary lysine restriction and arginine enrichment should improve prognosis and avoid developmental delay and intellectual disability. The purpose of this review is to summarize briefly the latest reports on the etiology, clinical symptoms, diagnosis, and management of patients suffering from pyridoxine-dependent epilepsy

Novel 2-(Adamantan-1-ylamino)Thiazol-4(5H)-One Derivatives and Their Inhibitory Activity towards 11β-HSD1—Synthesis, Molecular Docking and In Vitro Studies

A common mechanism in which glucocorticoids participate is suggested in the pathogenesis of such metabolic diseases as obesity, metabolic syndrome, or Cushing’s syndrome. The enzyme involved in the control of the availability of cortisol, the active form of the glucocorticoid for the glucocorticoid receptor, is 11β-HSD1. Inhibition of 11β-HSD1 activity may bring beneficial results for the alleviation of the course of metabolic diseases such as metabolic syndrome, Cushing’s syndrome or type 2 diabetes. In this work, we obtained 10 novel 2-(adamantan-1-ylamino)thiazol-4(5H)-one derivatives containing different substituents at C-5 of thiazole ring and tested their activity towards inhibition of two 11β-HSD isoforms. For most of them, over 50% inhibition of 11β-HSD1 and less than 45% inhibition of 11β-HSD2 activity at the concentration of 10 µM was observed. The binding energies found during docking simulations for 11β-HSD1 correctly reproduced the experimental IC50 values for analyzed compounds. The most active compound 2-(adamantan-1-ylamino)-1-thia-3-azaspiro[4.5]dec-2-en-4-one (3i) inhibits the activity of isoform 1 by 82.82%. This value is comparable to the known inhibitor-carbenoxolone. The IC50 value is twice the value determined by us for carbenoxolone, however inhibition of the enzyme isoform 2 to a lesser extent makes it an excellent material for further tests

2-{[5-(Pyridin-4-yl)-4-p-tolyl-4H-1,2,4-triazol-3-yl]methyl}acrylic acid hemihydrate

The asymmetric unit of the title compound, 2C18H16N4O2·H2O, consists of two organic molecules and one solvent molecule. The symmetry-independent organic molecules have slightly different conformations: the 1,2,4-triazole ring forms dihedral angles of 84.61 (4), 89.68 (5) and 22.38 (6)°, respectively, with the 2-propenecarbocylic, p-tolyl and 4-pyridyl groups in one independent molecule, and 71.35 (4), 82.13 (5) and 24.82 (6)°, respectively, in the second. In the crystal, molecules ralated by the 21 screw axes are assembled via O—H...N and O—H...O hydrogen bonds into infinite chains and these are linked by further O—H...N hydrogen bonds into undulating sheets parallel to the bc plane. Adjacent sheets are connected by weak C—H...O interactions, forming a three-dimensional structure

A Review of the Biological Activity of Amidrazone Derivatives

Amidrazones are widely used in chemical synthesis, industry and agriculture. We compiled some of the most important findings on the biological activities of amidrazones described in the years 2010–2022. The data were obtained using the ScienceDirect, Reaxys and Google Scholar search engines with keywords (amidrazone, carbohydrazonamide, carboximidohydrazide, aminoguanidine) and structure strategies. Compounds with significant biological activities were included in the review. The described structures derived from amidrazones include: amidrazone derivatives; aminoguanidine derivatives; complexes obtained using amidrazones as ligands; and some cyclic compounds obtained from amidrazones and/or containing an amidrazone moiety in their structures. This review includes chapters based on compound activities, including: tuberculostatic, antibacterial, antifungal, antiparasitic, antiviral, anti-inflammatory, cytoprotective, and antitumor compounds, as well as furin and acetylocholinesterase inhibitors. Detailed information on the compounds tested in vivo, along the mechanisms of action and toxicity of the selected amidrazone derivatives, are described. We describe examples of compounds that have a chance of becoming drugs due to promising preclinical or clinical research, as well as old drugs with new therapeutic targets (repositioning) which have the potential to be used in the treatment of other diseases. The described examples prove that amidrazone derivatives are a potential source of new therapeutic substances and deserve further research

Latest developments in metal complexes as anticancer agents

Every year novel biologically active compounds are designed as antitumor agents. This review covers and highlights some of the most important findings described during 2018–2020 to appoint the benefits and drawbacks regarding the activity and toxicity of the metal-based cancer drug candidates. We review new multi-action platinum(IV) prodrugs and other metal complexes with high chemotherapeutic potential, which are designed to overcome cisplatin-resistant cancer cells. We also overview new complexes of Os(II), Ru(II), Ir(III), and Zn(II) used for photodynamic therapy, as well as the complexes conjugated with conventional drugs exhibiting new mechanisms of action. Promising complexes that exceed the selectivity of cisplatin, highly effective in vitro and in vivo, against certain types of neoplasms are distinguished in the lung, colon, liver, stomach, breast cancers and others

Evaluation of Anthelmintic and Anti-Inflammatory Activity of 1,2,4-Triazole Derivatives

Parasitic diseases, caused by intestinal helminths, remain a very serious problem in both human and veterinary medicine. While searching for new nematicides we examined a series of 1,2,4-triazole derivatives 9–22, obtained during reactions of N3-substituted amidrazones with itaconic anhydride. Two groups of compounds, 9–16 and 17–22, differed in the position of the double bond on the methacrylic acid moiety. The toxicity of derivatives 9–22 and the anti-inflammatory activity of 12 and 19–22 were studied on peripheral blood mononuclear cells (PBMC). Antiproliferative activity of compounds 12 and 19–22 was tested cytometrically in PBMC cultures stimulated by phytohemagglutinin. The influence of derivatives 12 and 19–22 on the TNF-α, IL-6, IL-10 and IFN-γ production was determined by ELISA in lipopolysaccharide-stimulated PBMC cultures. Anthelmintic activity of compounds 10–22 was studied in the Rhabditis sp. nematodes model. Most compounds (11–22) proved to be non-toxic to human PBMC. Derivatives 19–22 showed anti-inflammatory activity by inhibiting the proliferation of lymphocytes. Moreover, compounds 12 and 19–22 significantly reduced the production of TNF-α and derivatives 19–21 decreased the level of INF-γ. The strongest anti-inflammatory activity was observed for compound 21. Compounds 12 and 14 demonstrated anthelmintic activity higher than albendazole and may become promising candidates for anthelmintic drugs

Evaluation of Biological Activity of New 1,2,4-Triazole Derivatives Containing Propionic Acid Moiety

To this day, the quest to find new drugs is still a challenge due to the growing demands of patients suffering from chronic inflammatory diseases and the need for the individualization of therapy. The aim of this research was to synthesize new 1,2,4-triazole derivatives containing propanoic acid moiety and to investigate their anti-inflammatory, antibacterial and anthelmintic activity. Compounds 3a–3g were obtained in reactions of amidrazones 1a–1g with succinic anhydride. Several analyses of proton and carbon nuclear magnetic resonance (1H NMR, 13C NMR, respectively), as well as high-resolution mass spectra (HRMS), confirmed the structures of 1,2,4-triazole derivatives 3a–3g. Toxicity, antiproliferative activity and influence on cytokine release (TNF-α: Tumor Necrosis Factor-α, IL-6: Interleukin-6, IFN-γ: Interferon-γ, and IL-10: Interleukin-10) of the compounds 3a–3g were evaluated in peripheral blood mononuclear cells culture. Moreover, mitogen-stimulated cell culture was used for biological activity tests. The antimicrobial and anthelmintic activity of derivatives 3a–3g were studied against Gram-positive and Gram-negative bacterial strains and Rhabditis sp. culture. Despite the lack of toxicity, compounds 3a–3g significantly reduced the level of TNF-α. Derivatives 3a, 3c and 3e also decreased the release of IFN-γ. Taking all of the results into consideration, compounds 3a, 3c and 3e show the most beneficial anti-inflammatory effects

Synthesis and Structural Study of Amidrazone Derived Pyrrole-2,5-Dione Derivatives: Potential Anti-Inflammatory Agents

1H-pyrrole-2,5-dione derivatives are known for their wide range of pharmacological properties, including anti-inflammatory and antimicrobial activities. This study aimed to synthesize new 3,4-dimethyl-1H-pyrrole-2,5-dione derivatives 2a–2f in the reaction of N3-substituted amidrazones with 2,3-dimethylmaleic anhydride and evaluate their structural and biological properties. Compounds 2a–2f were studied by the 1H-13C NMR two-dimensional techniques (HMQC, HMBC) and single-crystal X-ray diffraction (derivatives 2a and 2d). The anti-inflammatory activity of compounds 2a–2f was examined by both an anti-proliferative study and a production study on the inhibition of pro-inflammatory cytokines (IL-6 and TNF-α) in anti-CD3 antibody- or lipopolysaccharide-stimulated human peripheral blood mononuclear cell (PBMC) cultures. The antibacterial activity of compounds 2a–2f against Staphylococcus aureus, Enterococcus faecalis, Micrococcus luteus, Esherichia coli, Pseudomonas aeruginosa, Yersinia enterocolitica, Mycobacterium smegmatis and Nocardia corralina strains was determined using the broth microdilution method. Structural studies of 2a–2f revealed the presence of distinct Z and E stereoisomers in the solid state and the solution. All compounds significantly inhibited the proliferation of PBMCs in anti-CD3-stimulated cultures. The strongest effect was observed for derivatives 2a–2d. The strongest inhibition of pro-inflammatory cytokine production was observed for the most promising anti-inflammatory compound 2a

Polymorphism and Isostructurality of the Series of 3‑(4,5-Diaryl‑4<i>H</i>‑1,2,4-triazole-3-yl)propenoic Acid Derivatives

Polymorphism of four biologically active 3-(4,5-diaryl-4<i>H</i>-1,2,4-triazole-3-yl)­propenoic acid derivatives has been investigated. Traditional solution-based solid-state forms screening revealed three anhydrous forms of 3-[4-phenyl-5-(2-pyridyl)-4<i>H</i>-1,2,4-triazole-3-yl]­propenoic acid. Noteworthy, two pairs of concomitant polymorphs were detected for this system. Two other compounds were found to be dimorphic. The molecular and crystal structures of all obtained crystal forms were established by single-crystal X-ray diffraction. The resulting crystal structures were analyzed in terms of molecular conformation, intermolecular interaction patterns, and crystal packing motifs. The experimental studies were supported by extended lattice and interaction energy calculations. It was found that the carboxylic group adopts the <i>anti</i> conformation in all studied forms and is involved in the intramolecular O–H···N_triazole hydrogen bonding. In consequence, the association modes are dominated by the weak C–H···O, C–H···N hydrogen bonds further supported by effective π-stacking interactions between the overlapping triazole-propenoic acid units. Substantial conformational differences between polymorphs result from rotation around the triazole-aryl bonds. The thermodynamic relationships between polymorphs were investigated by variable-temperature powder diffraction and differential scanning calorimetry. The studies revealed four pairs of enantiotropically related polymorphs. Transformations between the polymorphs occur in the single-crystal-to-single-crystal mode