Transition metal complexes with thiosemicarbazide-based ligands. Part 60. Reactions of copper(II) bromide with pyridoxal S-methylisothiosemicarbazone (PLITSC). Crystal structure of [Cu(PLITSC−H)H2O]Br•H2O

The synthesis and structural characterization of a square-planar copper(II) complex with pyridoxal S-methylisothiosemicarbazone (PLITSC) of the formula [Cu(PLITSC−H)H2O]Br•H2O (1) as the first Cu(II) complex with monoanionic form of this ligand were described. Complex 1 together with two previously synthesized complexes [Cu(PLITSC)Br2] (2) and [Cu(PLITSC)Br(MeOH)]Br (3) were characterized by elemental analysis, IR and electronic spectra and also by the methods of thermal analysis, conductometry and magnetochemistry. [Projekat Pokrajisnkog sekretarijata za nauku i tehnoloski razvoj Vojvodine i Ministarstva nauke Republike Srbije, br. 172014

Molecular Mechanisms of Resistance to Immune Checkpoint Inhibitors in Melanoma Treatment: An Update

Over the past decade, immune checkpoint inhibitors (ICI) have revolutionized the treatment of advanced melanoma and ensured significant improvement in overall survival versus chemotherapy. ICI or targeted therapy are now the first line treatment in advanced melanoma, depending on the tumor v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutational status. While these new approaches have changed the outcomes for many patients, a significant proportion of them still experience lack of response, known as primary resistance. Mechanisms of primary drug resistance are not fully elucidated. However, many alterations have been found in ICI-resistant melanomas and possibly contribute to that outcome. Furthermore, some tumors which initially responded to ICI treatment ultimately developed mechanisms of acquired resistance and subsequent tumor progression. In this review, we give an overview of tumor primary and acquired resistance mechanisms to ICI and discuss future perspectives with regards to new molecular targets and combinatorial therapies

Pre-prosthetic Treatment o of a 35-Year-Old Patient with Poor Oral Health: A Case Report

This is a case of a 35-year-old patient who was selected to participate in the humanitarian project of a complete oral rehabilitation and quality of life improvement. The project was carried out by the dean, professors, teaching assistants and students at the Faculty of Dental Medicine and Health in Osijek. Patient’s oral cavity status was incongruent with his age due to the extensive inflammatory disease and active caries on multiple teeth. Further progression of dental disease in this patient would have led to a complete loss of function, alveolar ridge resorption and edentulousness of the both laws. Clinical examination revealed the following: decay of the teeth 18, 13, 12, 23, 33, 43 (FDI system), dental attrition of teeth 32, 31, 41, 42, root remnants 15, 14, 11, 24, 26, 27, 38, 37, 36, 35 and 34, periodontitis and periapical periodontitis. Extensive dental reparative work has been done in this patient and he was prepared for the upcoming prosthetic work

(E)-4-[(2-Carbamoylhydrazinylidene)methyl]-3-hydroxy-5-hydroxymethyl-2-methylpyridin-1-ium nitrate

The title compound, C9H13N4O3+center dot NO3-, is the first structurally characterized Schiff base derived from semicarbazide and pyridoxal. Unusually for an unsubstituted semicarbazone, the compound adopts a syn conformation, in which the carbonyl O atom is in a cis disposition relative to the azomethine N atom. This arrangement is supported by a pair of hydrogen bonds between the organic cation and the nitrate anion. The cation is essentially planar, with only a hydroxymethyl O atom deviating significantly from the mean plane of the remaining atoms (r.m.s. deviation of the remaining non-H atoms = 0.01 angstrom). The molecules are linked into flat layers by N-H center dot center dot center dot O and C-H center dot center dot center dot O hydrogen bonds. O-H center dot center dot center dot O hydrogen bonds involving the hydroxymethyl group as a donor interconnect the layers into a three-dimensional structure

Transition metal complexes with thiosemicarbazide-based ligands. Part 61. Comparative analysis of structural properties of the pyridoxal thiosemicarbazone ligands. Crystal structure of PLTSC center dot HCl center dot 2H(2)O and its complex [Fe(PLTSC)Cl-2(H2O)]Cl

A novel pyridoxal thiosemicarbazone (PLTSC) compound, exhibiting ligating properties, of the formula PLTSC center dot HCl center dot 2H(2)O (1) was synthesized and characterized by X-ray analysis. The PLTSC ligand 1 displays significantly different conformation in comparison to the five previously reported compounds of this type. The structural properties of six PLTSC ligands in different conformations were compared in order to establish the structural differences and understand the factors that facilitate particular conformations. The analysis indicated great structural flexibility of the PLTSC ligands. The PLTSC ligand 1 is essentially a planar molecule with the r.m.s deviation of all non-H atoms equal to 0.06 angstrom. Consequently, the molecules of 1 form a layered three-dimensional structure which is stabilized by a variety of hydrogen bonds: O-H center dot center dot center dot O, O-H center dot center dot center dot N, O-H center dot center dot center dot Cl, O-H center dot center dot center dot S, N-H center dot center dot center dot O, N-H center dot center dot center dot N, N-H center dot center dot center dot Cl, N-H center dot center dot center dot S. In addition, the crystal structure of the Fe(III) complex with the ligand 1 of the formula [Fe(PLTSC)Cl-2(H2O)]Cl was resolved by single-crystal X-ray analysis and structural properties of this octahedral complex were discussed and compared to those of uncoordinated PLTSC ligand

Impact of Breast Density Awareness on Knowledge about Breast Cancer Risk Factors and the Self-Perceived Risk of Breast Cancer

Breast density (BD) reduces sensitivity of mammography, and is a strong risk factor for breast cancer (BC). Data about women’s awareness and knowledge of BD are limited. Our aim is to examine whether the BD information disclosure and BD awareness among women without BC are related to their knowledge about BC risk factors. We examined self-reported BC risk perception and its association to BD awareness and level of health literacy. A cross-sectional, single site study included 263 Croatian women without BC who had mammographic examination. Data were collected by interviews using questionnaires and a validated survey. Of the total, 77.1% had never heard of BD, and 22.9% were aware of their BD. Most participants who knew their BD (88.2%, p < 0.001) had higher levels of education. Majority of subjects (66.8%) had non-dense breasts and 33.2% had dense breasts. Subjects aware of their BD knew that post-menopausal hormone replacement therapy (p = 0.04) and higher BD (p = 0.03) are BC risk factors. They could more easily access information about health promotion (p = 0.03). High-BD informed women assessed their lifetime BC risk as significantly higher than all others (p = 0.03). Comprehension of BD awareness and knowledge is crucial for reinforcement of educational strategies and development of amendatory BC screening decisions

Synthesis, characterization and antitumor activity of polymeric copper(II) complexes with thiosemicarbazones of 3-methyl-5-oxo-1-phenyl-3-pyrazolin-4-carboxaldehyde and 5-oxo-3-phenyl-3-pyrazolin-4-carboxaldehyde

New polymeric copper(II) complexes with two tridentate ONS thiosemicarbazone ligands containing substituted pyrazolone moiety were synthesized and characterized by means of spectroscopic, electrochemical and crystallographic techniques. While both ligands exist as different tautomers in the solid state and DMSO-d(6) solution, Cu(II) ion coordinates the ligands from the same tautomeric form with square-pyramidal geometry around each Cu atom. In the crystal structures, the copper(II) complex cation forms polymeric chains {[Cu(L)Cl+]}(n) with a bridging chlorine atom. One of the complexes was found to have a significantly higher cytotoxic potential in comparison with cisplatin in inhibition of several cell lines (HL60, REH, C6, L929 and B16). The results obtained on the basis of flow cytometry indicated that apoptosis could be possible mechanism of cell death