Cytotoxic activities of new iron(III) and nickel(II) chelates of some S-methyl-thiosemicarbazones on K562 and ECV304 cells

The S-methyl-thiosemicarbazones of the 2- hydroxy-R-benzaldehyde (R= H, 3-OH 3-OCH3 or 4-OCH3) reacted with the corresponding aldehydes in the presence of FeCl3 and NiCl2. New ONNO chelates of iron(III) and nickel (II) with hydroxy- or methoxy-substitued N1,N4-diarylidene-Smethyl- thiosemicarbazones were characterized by means of elemental analysis, conductivity and magnetic measurements, UV-Vis, IR and 1H-NMR spectroscopies. Cytotoxic activities of the compounds were determined using K562 chronic myeloid leukemia and ECV304 human endothelial cell lines by MTT assay. It was determined that monochloro N1-4- methoxysalicylidene-N4-4-methoxysalicylidene-S-methylthiosemicarbazidato- iron(III) complex showed selective anti-leukemic effects in K562 cells while has no effect in ECV304 cells in the 0.53 μg/ml (IC50) concentrations. Also, some methoxy-substitued nickel(II) chelates exhibit high cytotoxic activitiy against both of these cell lines in low concentrations. Cytotoxicity data were evaluated depending on cell lines origin and position of the substituents on aromatic rings

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Iron(III) and nickel(ii) complexes as potential anticancer agents: Synthesis, physicochemical and structural properties, cytotoxic activity and DNA interactions

Template reactions of 2-hydroxy-R-benzaldehyde-S-methylisothiosemicarbazones (R = 3-methoxy or 4-hydroxy) with the corresponding aldehydes in the presence of FeCl3 and NiCl2 yielded N1,N4-disalicylidene chelate complexes. The compounds were characterized by means of elemental and spectroscopic methods. The structure of complex 1 was determined by X-ray single crystal diffraction. Crystal data (Mo K?; 296 K) are as follows: monoclinic space group P21/c, a = 12.9857(8) Å, b = 7.8019(4) Å, c = 19.1976(12) Å, ß = 101.655(5)°, Z = 4. Cytotoxic effects of the compounds were evaluated by the MTT assay in K562 leukemia, ECV304 endothelial and normal mononuclear cells, and DNA fragmentation analysis using the diphenylamine reaction was performed. The DNA binding capacity of thiosemicarbazones at IC50 and different concentrations was investigated. The DNA fragmentation percentage of compound treated cells was higher than that of non-treated control cells but was higher for compound 3 (84%) compared to the others. The interaction of compounds 1-4 and DNA was investigated voltammetrically by using nucleic acid modified electrodes after the double stranded fish sperm DNA (fsDNA), or poly(dA)·poly(dT), was immobilized onto the surface of pencil graphite electrodes (PGEs). Accordingly, the oxidation signals of DNA bases, guanine and adenine, were measured by using differential pulse voltammetry (DPV). The changes in the signals of guanine and adenine were evaluated before and after the interaction process. The results indicated that compound 3 was cytotoxic at very low concentrations in K562 leukemia cells unlike other cells and that could damage the DNA double stranded form, specifically the adenine base. Therefore, it may have a selective antileukemic effect and drug potential. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015