A5063264676- Drug Transport and Resistance Mechanisms
- Metal complexes synthesis and properties
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Computational Drug Discovery Methods
- Radiopharmaceutical Chemistry and Applications
- Nanoparticle-Based Drug Delivery
- Trace Elements in Health
- Cancer therapeutics and mechanisms
- Molecular Sensors and Ion Detection
- Pain Mechanisms and Treatments
- Redox biology and oxidative stress
- Ion Channels and Receptors
- Iron Metabolism and Disorders
- Cancer-related gene regulation
- Peroxisome Proliferator-Activated Receptors
- Synthesis and Characterization of Heterocyclic Compounds
- Bioactive Compounds and Antitumor Agents
- Metabolism, Diabetes, and Cancer
- Endoplasmic Reticulum Stress and Disease
- Adenosine and Purinergic Signaling
- Biochemical effects in animals
- Connexins and lens biology
- Synthesis and Reactions of Organic Compounds
- Eicosanoids and Hypertension Pharmacology
Semmelweis University
2018-2023
HUN-REN Research Centre for Natural Sciences
2014-2022
Institute of Molecular Life Sciences
2014-2022
Hungarian Research Network
2022
Hungarian Academy of Sciences
2016-2020
University of Bonn
2011-2016
Philipps University of Marburg
2011
A recently proposed strategy to overcome multidrug resistance (MDR) in cancer is target the collateral sensitivity of otherwise resistant cells. We designed a library 120 compounds explore chemical space around previously identified 8-hydroxyquinoline-derived Mannich bases with robust MDR-selective toxicity. included study effect halogen and alkoxymethyl substitutions R5 combination different R7, shift base from R7 R5, as well introduction an aromatic moiety. Cytotoxicity tests performed on...
Abstract Due to their high biological activity, thiosemicarbazones have been developed for treatment of diverse diseases, including cancer, resulting in multiple clinical trials especially the lead compound Triapine. During last years, a novel subclass anticancer has attracted substantial interest based on enhanced cytotoxic activity. Increasing evidence suggests that double-dimethylated Triapine derivative Me 2 NNMe differs from not only its efficacy but also mode action. Here we show -...
Due to their significant biological activity, thiosemicarbazones (TSCs) are promising candidates for anticancer therapy. In part, the efficacy of TSCs is linked ability chelate essential metal ions such as copper and iron. Triapine, best-studied TSC, has been tested clinically with results in hematological diseases. During past few years, a novel subclass improved activity was found induce paraptosis, recently characterized form cell death. The aim this study identify structural chemical...
Solution stability, chloride ion affinity and multidrug resistance selectivity of half-sandwich Rh(η<sup>5</sup>-C<sub>5</sub>Me<sub>5</sub>) Ru(η<sup>6</sup>-<italic>p</italic>-cymene) complexes 8-hydroxyquinolines.
Despite significant progress, resistance to chemotherapy is still the main reason why cancer remains a deadly disease. An attractive strategy target collateral sensitivity of otherwise multidrug resistant (MDR) cancer. In this study, our aim was catalog various compounds that were reported elicit increased toxicity in P-glycoprotein (Pgp)-overexpressing MDR cells. We show activity most serendipitously identified cells fact cell-line specific, and not influenced significantly by function Pgp....
A relationship between p<italic>K</italic><sub>a</sub> values, binding abilities to copper(<sc>ii</sc>) and iron(<sc>iii</sc>) anticancer activity of 8-hydroxyquinoline derived Mannich bases.
Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a ligand-regulated nuclear with essential functions in metabolism and inflammation. We have synthesized new derivative [methyl 3-(<i>N</i>-(4-(hexylamino)-2-methoxyphenyl)sulfamoyl)thiophene-2-carboxylate (ST247) structurally related to the published PPARβ/δ inhibitory ligand methyl 3-(<i>N</i>-(2-methoxy-4-(phenylamino)phenyl)sulfamoyl)thiophene-2-carboxylate (GSK0660). ST247 has higher affinity than GSK0660, at equimolar...
Abstract Clinical evidence shows that following initial response to treatment, drug-resistant cancer cells frequently evolve and, eventually, most tumors become resistant all available therapies. We compiled a focused library consisting of &gt;500 commercially or newly synthetized 8-hydroxyquinoline (8OHQ) derivatives whose toxicity is paradoxically increased rather than decreased by the activity P-glycoprotein (Pgp), transporter conferring multidrug resistance (MDR). Here, we deciphered...
α-N-Heterocyclic thiosemicarbazones are an important class of investigational anticancer drugs. The most prominent representative is 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine), which has shown promising results in clinical trials and currently evaluated phase III. In this study, we investigated the influence a chalcogen atom exchange from S (Triapine) to O (O-Triapine) Se (Se-Triapine) methylation hydrazonic NH moiety (Me-Triapine) on their complexation with Fe(ii),...
Synthesis of organometallic half-sandwich polypyridyl Ru and Rh complexes. Anticancer activity against resistant cancer cell lines effects ligand methylation on aqueous chemistry structure.
Three novel pyrimidinylhydrazones substituted at either the aromatic moiety or imine carbon atom were synthesized and characterized by standard analytical methods. All compounds found to be toxic in micro- submicromolar range against a diverse panel of cancer cell lines including multidrug resistant (MDR) derivatives expressing P-glycoprotein (Pgp). UV–visible spectrophotometry experiments demonstrated that most active compound (3) forms highly stable complexes with iron(III) copper(II) wide...
Abstract GSK0660 ( 1 ) is the first peroxisome proliferator‐activated receptor (PPAR) β / δ ‐selective inhibitory ligand described in literature. Based on its structure, we designed and synthesized a series of modified compounds to establish preliminary structure–activity relationships. Most beneficial for increased binding affinity towards PPAR domain was replacement 4′‐aminophenyl substituent by medium‐length n ‐alkyl chains, such as ‐butyl or iso ‐pentyl. These show activity down...
Resistance to chemotherapeutic agents is a major obstacle in cancer treatment. A recently proposed strategy target the collateral sensitivity of multidrug resistant (MDR) cancer. Paradoxically, toxicity certain metal chelating increased, rather than decreased, by function P-glycoprotein (Pgp), which known confer resistance effluxing compounds from cells. We have characterized and compared solution’s chemical properties including ligand protonation binding set structurally related...
Keratinocytes of the mammalian skin provide not only mechanical protection for tissues, but also transmit mechanical, chemical, and thermal stimuli from external environment to sensory nerve terminals. Sensory fibers penetrate epidermal basement membrane function in tight intercellular space among keratinocytes. Here we show that keratinocytes produce hydrogen peroxide upon activation NADPH oxidase dual 1 (DUOX1). This enzyme can be activated by increasing cytosolic calcium levels. Using...
Abstract Molecular descriptor (2D) and three dimensional (3D) shape based similarity methods are widely used in ligand virtual drug design. In the present study pairwise structure comparisons among a set of 4858 DTP compounds tested NCI60 tumor cell line anticancer screen were computed using chemical hashed fingerprints 3D molecule shapes to calculate 2D similarities, respectively. Additionally, biological activity similarities calculated by correlating 60 element vectors pGI50 values...
Comprehensive analysis of post-translation modifications (PTMs) is an important mission proteomics. However, the consideration PTMs increases search space and may therefore impair efficiency protein identification. Using thousands proteomic searches, we investigated practical aspects considering multiple in Byonic searches for maximization peptide hits. The inclusion all PTMs, which occur with at least 2% frequency sample, has advantageous effect on A linear relationship was established...
Peroxidasin (PXDN) is involved in the crosslinking of collagen IV, a major constituent basement membranes. Disruption membrane integrity as observed genetic alterations IV or PXDN can result developmental defects and diverse pathologies. Hence, study activity (patho)physiological contexts highly relevant. So far, measurements have been reported from purified proteins, cell lysates de-cellularized extracellular matrix. Here, for first time we report measurement live cells using Amplex Red...
<div>Abstract<p>Despite significant progress, resistance to chemotherapy is still the main reason why cancer remains a deadly disease. An attractive strategy target collateral sensitivity of otherwise multidrug resistant (MDR) cancer. In this study, our aim was catalog various compounds that were reported elicit increased toxicity in P-glycoprotein (Pgp)–overexpressing MDR cells. We show activity most serendipitously identified cells fact cell-line specific, and not influenced...
<div>Abstract<p>Despite significant progress, resistance to chemotherapy is still the main reason why cancer remains a deadly disease. An attractive strategy target collateral sensitivity of otherwise multidrug resistant (MDR) cancer. In this study, our aim was catalog various compounds that were reported elicit increased toxicity in P-glycoprotein (Pgp)–overexpressing MDR cells. We show activity most serendipitously identified cells fact cell-line specific, and not influenced...
<div>Abstract<p>Clinical evidence shows that following initial response to treatment, drug-resistant cancer cells frequently evolve and, eventually, most tumors become resistant all available therapies. We compiled a focused library consisting of >500 commercially or newly synthetized 8-hydroxyquinoline (8OHQ) derivatives whose toxicity is paradoxically increased rather than decreased by the activity P-glycoprotein (Pgp), transporter conferring multidrug resistance (MDR)....
<p>Supplementary tables and figures, supplementary materials methods</p>