Antitumor Metallothiosemicarbazonates: Structure and Antitumor Activity of Palladium Complex of Phenanthrenequinone Thiosemicarbazone

The crystal structure of the potential antitumor metal compound, viz. chloro, mono(phenanthrenequinone thiosemicarbazonato) palladium(II) dimethyl formamide solvate, is reported. The central palladium(II) atom is in a square planar environment provided by the tridentate, monoanionic thiosemicarbazone ligand and the ancillary chloride ion. The compound exhibited remarkable activity against drug-sensitive and drug-resistant breast cancer cell lines and was relatively nontoxic toward the normal mammary epithelial cells. The drug-induced killing effect against breast cancer cell lines was predominantly mediated via apoptosis, a physiologic form of cell death

Machine Learning Approach with Harmonized Multinational Datasets for Enhanced Prediction of Hypothyroidism in Patients with Type 2 Diabetes

Type 2 diabetes (T2D) is a global health concern with increasing prevalence. Comorbid hypothyroidism (HT) exacerbates kidney, cardiac, neurological and other complications of T2D; these risks can be mitigated pharmacologically upon detecting HT. The current HT standard of care (SOC) screening in T2D is infrequent, delaying HT diagnosis and treatment. We present a first-to-date machine learning algorithm (MLA) clinical decision tool to classify patients as low vs. high risk for developing HT comorbid with T2D; the MLA was developed using readily available patient data from harmonized multinational datasets. The MLA was trained on data from NIH All of US (AoU) and UK Biobank (UKBB) (Combined dataset) and achieved a high negative predictive value (NPV) of 0.989 and an AUROC of 0.762 in the Combined dataset, exceeding AUROCs for the models trained on AoU or UKBB alone (0.666 and 0.622, respectively), indicating that increasing dataset diversity for MLA training improves performance. This high-NPV automated tool can supplement SOC screening and rule out T2D patients with low HT risk, allowing for the prioritization of lab-based testing for at-risk patients. Conversely, an MLA output that designates a patient to be at risk of developing HT allows for tailored clinical management and thereby promotes improved patient outcomes

Appended 1,2-naphthoquinones as Anticancer Agents 1: Synthesis, Structural, Spectral and Antitumor Activities of Ortho-naphthaquinone Thiosemicarbazone and its Transition Metal Complexes

Copper(II), nickel(II), palladium(II) and platinum(II) complexes of ortho-naphthaquinone thiosemicarbazone were synthesized and characterized by spectroscopic studies. In both solution (NMR) and solid state (IR, single-crystal X-ray diffraction determination) the free ligand NQTS exists as the thione form. The Pd complex (X-ray) crystallizes as the H-bonded dimer, [Pd(NQTS)Cl]2·2DMSO, where palladium(II) coordinates in a square planar configuration to the monodeprotonated, tridentate thiosemicarbazone ligand. The nickel(II) complex shows 1:2 metal to ligand stoichiometry while the other complexes exhibit 1:1 metal-ligand compositions. In vitro anticancer studies on MCF7 human breast cancer cells reveal that adding a thiosemicarbazone pharmacophore to the parent quinone carbonyl considerably enhances its antiproliferative activity. Among the metal complexes, the nickel compound exhibits the lowest IC50 value (2.25 µM) suggesting a different mechanism of action involving inhibition of topoisomerase II activity

DC & transient circuit simulation methodologies for organic electronics

This work establishes a novel circuit simulation methodology for organic thin film transistors (OTFTs). Because of a lack of well developed physical models for OTFTs and due to the limitations of conventional parameter extraction techniques, the approaches presented in this work come in handy for circuit designers. The first approach uses a look-up table (LUT) model, which is implemented in a general purpose public-domain circuit simulator SEQUEL (solver for circuit equations with user-defined elements). In the second approach, circuit simulation is performed using equivalent SPICE parameters, which are extracted using a global optimization technique namely particle swarm optimization (PSO) algorithm. A good match has been observed between LUT simulations and SPICE based circuit simulations for both DC and transient cases