Structural characterization and antitumor activity of platinum(II) complexes with phenothiazine and N-methylphenothiazine

Cisplatin is one of the most used anticancer agents, and along with carboplatin and oxaliplatin, is a part of more than 50% of clinically applied anticancer regimens [1]. However, the side effects of cisplatin are severe and include dose-limiting toxicity, such as neurotoxicity, nephrotoxicity and ototoxicity. Platinum(II) complexes with different structure from cisplatin provide many opportunities for design of novel antitumor drugs with improved pharmacological properties. Considering this, in the present study, new platinum(II) complexes with phenothiazine (phtz) and N-methylphenothiazine (N-Mephtz), [PtCl2(phtz)(CH3CN)] (1) and [PtCl2(N-Mephtz)(CH3CN)] (2), were synthesized. These complexes were characterized by elemental microanalysis, NMR (1H and 13C) and IR spectroscopic measurements, while the structure of complex 1 was determined by single-crystal X-ray diffraction analysis. The antitumor activity of the platinum(II) complexes was tested in vitro against a panel of human cancer cell lines, including A549 (lung cancer), A375 (melanoma, skin cancer), MDA-MB-231 (breast cancer), and HCT116 (colon cancer). To check the selectivity of the synthesized complexes 1 and 2, a healthy MRC-5 cell line (lung fibroblasts) was also included in this study.Book of abstract:16th International Symposium on Applied Bioinorganic Chemistry (16-ISABC) 11-14th June University of Ioannina Greec

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

Do health reforms impact cost consciousness of health care professionals? Results from a Nation-wide survey in the Balkans

© 2016 Trakya University Faculty of Medicine. Background: Serbia, as the largest market of the Western Balkans, has entered socioeconomic transition with substantial delay compared to most of Eastern Europe. Its health system reform efforts were bold during the past 15 years, but their results were inconsistent in various areas. The two waves of global recession that hit Balkan economies ultimately reflected to the financial situation of healthcare. Serious difficulties in providing accessible medical care to the citizens became a reality. A large part of the unbearable expenses actually belongs to the overt prescription of pharmaceuticals and various laboratory and imaging diagnostic procedures requested by physicians. Therefore, a broad national survey was conducted at all levels of the healthcare system hierarchy to distinguish the ability of cost containment strategies to reshape clinician’s mindsets and decision-making in practice. Aims: Assessment of healthcare professionals’ judgment on economic consequences of prescribed medical interventions and evaluation of responsiveness of healthcare professionals to policy measures targeted at increasing cost-consciousness. Study Design: Cross-sectional study. Methods: A nationwide cross-sectional survey was conducted through a hierarchy of medical facilities across diverse geographical regions before and after policy action, from January 2010 to April 2013. In the middle of the observed period, the National Health Insurance Fund (RFZO) adopted severe cost-containment measures. Independently, pharmacoeconomic guidelines targeted at prescribers were disseminated. Administration in large hospitals and community pharmacies was forced to restrict access to high budget-impact medical care. Economic Awareness of Healthcare Professionals Questionnaire–29 (EAHPQ-29), developed in Serbian language, was used in face-to-face interviews. The questionnaire documented clinician’s attitudes on: Clinical-Decision-Makingbetween- Alternative-Interventions (CDMAI), Qualityof- Health-Care (QHC), and Cost-Containment-Policy (CCP). The authors randomly and anonymously recruited 2000 healthcare experts, with a total of 1487 responding; after eliminating incomplete surveys, 649 participants were considered before and 651 after policy intervention. Results: Dentists (1.195±0.560) had a higher mean CDMAI score compared to physicians (1.017±0.453). Thesurgical group compared to the internist group had a higher total EAHPQ-29 score, CCP score and CDMAI score. Policy intervention had a statistically significant negative impact on the QHC score (F=4.958; df=1; p=0.027). There was no substantial impact of policy interventions on professional behavior and judgment with regard to the CDMAI, CCP, and total EAHPQ-29 scores. Conclusion: Although cost savings were forcibly imposed in practice, the effects on clinical decision-making weremodest. Clinicians’ perceptions of quality of medical care were explained in a less effective manner due to the severely constrained resources allocated to the providers. This pioneering effort in the Balkans exposes the inefficiency of current policies to expand clinicians’ cost consciousness