Therapeutic Consequences and Prognostic Impact of Multimorbidity in Heart Failure: Time to Act.

: In heart failure (HF) with reduced ejection fraction (HFrEF), the early diagnosis and proper treatment of comorbidities (CMs) are of fundamental relevance. Our aim was to assess the prevalence of CMs among real-world patients requiring hospitalisation for HFrEF and to investigate the effect of CMs on the implementation of guideline-directed medical therapy (GDMT) and on all-cause mortality (ACM). : The data of a consecutive HFrEF patient cohort hospitalised for HF between 2021 and 2024 were analysed retrospectively.

Novel Piperazine Derivatives of Vindoline as Anticancer Agents.

A series of novel vindoline-piperazine conjugates were synthesized by coupling 6 -substituted piperazine pharmacophores at positions 10 and 17 of alkaloid monomer vindoline through different types of linkers. The in vitro antiproliferative activity of the 17 new conjugates was investigated on 60 human tumor cell lines (NCI60). Nine compounds presented significant antiproliferative effects.

Transaminase-catalysis to produce trans-4-substituted cyclohexane-1-amines including a key intermediate towards cariprazine.

Cariprazine-the only single antipsychotic drug in the market which can handle all symptoms of bipolar I disorder-involves trans-4-substituted cyclohexane-1-amine as a key structural element. In this work, production of trans-4-substituted cyclohexane-1-amines was investigated applying transaminases either in diastereotope selective amination starting from the corresponding ketone or in diastereomer selective deamination of their diasteromeric mixtures. Transaminases were identified enabling the conversion of the cis-diastereomer of four selected cis/trans-amines with different 4-substituents to the corresponding ketones.

The effect of kidney function on guideline-directed medical therapy implementation and prognosis in heart failure with reduced ejection fraction.

Background: Kidney dysfunction (KD) is a main limiting factor of applying guideline-directed medical therapy (GDMT) and reaching the recommended target doses (TD) in heart failure (HF) with reduced ejection fraction (HFrEF).

Hypothesis: We aimed to assess the success of optimization, long-term applicability, and adherence of neurohormonal antagonist triple therapy (TT:RASi [ACEi/ARB/ARNI] + βB + MRA) according to the KD after a HF hospitalization and to investigate its impact on prognosis.

Methods: The data of 247 real-world, consecutive patients were analyzed who were hospitalized in 2019-2021 for HFrEF and then were followed-up for 1 year.

The Impact of Specialised Heart Failure Outpatient Care on the Long-Term Application of Guideline-Directed Medical Therapy and on Prognosis in Heart Failure with Reduced Ejection Fraction.

(1) Background: Besides the use of guideline-directed medical therapy (GDMT), multidisciplinary heart failure (HF) outpatient care (HFOC) is of strategic importance in HFrEF. (2) Methods: Data from 257 hospitalised HFrEF patients between 2019 and 2021 were retrospectively analysed. Application and target doses of GDMT were compared between HFOC and non-HFOC patients at discharge and at 1 year.

Triterpenes from as Cytotoxic Agents and Chemosensitizers to Overcome Multidrug Resistance of Cancer Cells.

The detailed mycochemical analysis of the -hexane extract of led to the isolation of four new lanostane diesters, named pholiols A-D (-), together with an acyclic triterpene, (3,6,10,14,18,22)-2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene (), ergosterol (), and 3β-hydroxyergosta-7,22-diene (). The isolation was carried out by multistep flash chromatography, and the structures were elucidated using extensive spectroscopic analyses, including 1D and 2D NMR and MS measurements. The isolated metabolites (-) were investigated for cytotoxic activity against Colo205 and Colo320 colon adenocarcinoma and nontumoral MRC-5 cell lines.

Synthesis of Novel Vindoline-Chrysin Hybrids.

Vinca alkaloids are well-known microtubule targeting agents, which are used against some types of cancer. Vindoline is one of the monomeric Vinca alkaloids which does not have anti-tumor effect, although its derivatives have serious impact on the field of these indole alkaloids. Chrysin is a secondary plant metabolite, which has broad-spectrum biological activity, among others anticancer activity.

Antimicrobial, Antioxidant and Antiproliferative Secondary Metabolites from .

is a sterile conk which produces macrofungus, a neglected Central-Eastern European relative of the prized , also known as chaga. Investigation of the methanol extract of the poroid fungus resulted in the isolation of citropremide (), 3,4-dihydroxybenzalacetone () , lanosterol (), ergost-6,8,22-trien-3β-ol (), and ergosterol peroxide (). The structures of fungal compounds were determined on the basis of one- and two-dimensional NMR and MS spectroscopic analysis.

Theoretical Design, Synthesis, and In Vitro Neurobiological Applications of a Highly Efficient Two-Photon Caged GABA Validated on an Epileptic Case.

In this paper, we present an additional, new cage-GABA compound, called 4-amino-1-(4'-dimethylaminoisopropoxy-5',7'-dinitro-2',3'-dihydro-indol-1-yl)-1-oxobutane-γ-aminobutyric acid (iDMPO-DNI-GABA), and currently, this compound is the only photoreagent, which can be applied for GABA uncaging without experimental compromises. By a systematic theoretical design and successful synthesis of several compounds, the best reagent exhibits a high two-photon efficiency within the 700-760 nm range with excellent pharmacological behavior, which proved to be suitable for a complex epileptic study. Quantum chemical design showed that the optimal length of the cationic side chain enhances the two-photon absorption by 1 order of magnitude due to the cooperating internal hydrogen bonding to the extra nitro group on the core.

Diversity-oriented synthesis through gamma radiolysis: Preparation of unusual ecdysteroid derivatives activating Akt and AMPK in skeletal muscle cells.

Gamma-ray radiation is a unique way to induce chemical transformations of bioactive compounds. In the present study, we pursued this approach to the diversity-oriented synthesis of analogs of 20-hydroxyecdysone (20E), an abundant ecdysteroid with a range of beneficial, non-hormonal bioactivities in mammals including humans. Gamma irradiations of aqueous solutions of 20E were conducted either in N- or NO-saturated solutions.

Novel Ring Systems: Spiro[Cycloalkane] Derivatives of Triazolo- and Tetrazolo-Pyridazines.

In orderto synthesize new pyridazine derivatives anellated with different nitrogen heterocyclic moieties, spiro[cycloalkane]pyridazinones were transformed into the corresponding thioxo derivatives via a reaction with phosphorus pentasulfide. The reaction of the formed 2,3-diazaspiro[5.5] undec-3-ene-1-thiones with hydrazine provided the corresponding 1-hydrazono-2,3-diazaspiro[5.

Triterpenes and Phenolic Compounds from the Fungus : Isolation, Structure Determination and Biological Activity.

Investigation of the methanol extract of the poroid fungus resulted in the isolation of a novel triterpene, fuscoporic acid (), together with inoscavin A and its previously undescribed isomer ( and ), 3,4-dihydroxy-benzaldehide (), osmundacetone (), senexdiolic acid (), natalic acid (), and ergosta-7,22-diene-3-one (). The structures of fungal compounds were determined on the basis of NMR and MS spectroscopic analyses, as well as molecular modeling studies. Compounds , - were examined for their antibacterial properties on resistant clinical isolates, and cytotoxic activity on human colon adenocarcinoma cell lines.

Proportion of Patients Eligible for Cardiac Contractility Modulation: Real-Life Data from a Single-Center Heart Failure Clinic.

Introduction: Based on recently published randomized controlled trials, cardiac contractility modulation (CCM) seems to be an effective device-based therapeutic option in symptomatic chronic heart failure (HF) (CHF). The aim of the current study was to estimate what proportion of patients with CHF and left ventricular ejection fraction (LVEF) <50% could be eligible for CCM based on the inclusion criteria of the FIX-HF-5C trial.

Methods: Consecutive patients referred and followed up at our HF clinic due to HF with reduced or mid-range LVEF were retrospectively assessed.

AAPH or Peroxynitrite-Induced Biorelevant Oxidation of Methyl Caffeate Yields a Potent Antitumor Metabolite.

Hydroxycinnamic acids represent a versatile group of dietary plant antioxidants. Oxidation of methyl--coumarate () and methyl caffeate () was previously found to yield potent antitumor metabolites. Here, we report the formation of potentially bioactive products of and oxidized with peroxynitrite (ONOO¯), a biologically relevant reactive nitrogen species (RNS), or with α,α'-azodiisobutyramidine dihydrochloride (AAPH) as a chemical model for reactive oxygen species (ROS).

The impact of serum concentration-guided digoxin therapy on mortality of heart failure patients: A long-term follow-up, propensity-matched cohort study.

Background: Recently published studies suggested that digoxin may increase mortality in heart failure with reduced ejection fraction (HFrEF). However, in the vast majority of former trials serum digoxin concentration (SDC) was not measured and therapy was not SDC-guided.

Aim: To assess the impact of SDC-guided digoxin therapy on mortality in HFrEF patients.

Discovery of New Heterocyclic Ring Systems as Novel and Potent V Receptor Antagonists.

Autism spectrum disorder is a neurodevelopmental disease with increasing occurrence. Recent studies focus on the development of novel V receptor antagonists which can influence the core symptoms of autism through the AVP pathway. In this study, we describe the synthesis of new heterocyclic ring systems.

Cerebrosides and Steroids from the Edible Mushroom with Antioxidant Potential.

The detailed chemical analysis of the methanol extract of (Pers.) P. Karst.

Synthesis and Cytotoxic Activity of New Vindoline Derivatives Coupled to Natural and Synthetic Pharmacophores.

New alkaloid derivatives were synthesized to improve the biological activity of the natural alkaloid vindoline. To this end, experiments were performed to link vindoline with various structural units, such as amino acids, a 1,2,3-triazole derivative, morpholine, piperazine and N-methylpiperazine. The structure of the new compounds was characterized by NMR spectroscopy and mass spectrometry (MS).

Synthesis and In Vitro Anticancer Evaluation of Novel Chrysin and 7-Aminochrysin Derivatives.

Chrysin is a naturally occurring flavonoid with mild anticancer activity. In this paper we report the synthesis of new chrysin derivatives alkylated with -phenylchloroacetamides in position 7. A novel method was developed for the preparation of 7-aminochrysin derivatives via the Smiles rearrangement, resulting in diphenylamine-type compounds.

Triterpenes from the Mushroom : Isolation, Structure Determination and Investigation in Bdelloid Rotifer Assays.

Twelve compounds (⁻) were isolated from the methanol extract of brick cap mushroom ( (Schaeff.) P. Kumm.

Antioxidant-Inspired Drug Discovery: Antitumor Metabolite Is Formed in Situ from a Hydroxycinnamic Acid Derivative upon Free-Radical Scavenging.

Cancer cells generally possess higher levels of reactive oxygen species than normal cells, and this can serve as a possible therapeutic target. In this proof-of-concept study, an antioxidant-inspired drug discovery strategy was evaluated using a hydroxycinnamic acid derivative. The processing of oxidized mixtures of p-coumaric acid methyl ester (pcm) revealed a new antitumor lead, graviquinone.

Attempted Synthesis of Alkaloids Condensed with Three-Membered Rings.

Our successful work for the synthesis of cyclopropanated vinblastine and its derivatives by the Simmons⁻Smith reaction was followed to build up further three-membered rings into the 14,15-position of the vindoline part of the dimer alkaloid. Halogenated 14,15-cyclopropanovindoline was prepared by reactions with iodoform and bromoform, respectively, in the presence of diethylzinc. Reactions of dichlorocarbene with vindoline resulted in the 10-formyl derivative.

Isolation and Structure Determination of Antiproliferative Secondary Metabolites from the Potato Earthball Mushroom, Scleroderma bovista (Agaricomycetes).

Mycochemical examination of a methanol extract of Scleroderma bovista Fr. (Agaricomycetes) led to the isolation of 7 compounds, which were, to our knowledge, identified for the first time in this species. The chemical structures of these compounds were determined through extensive spectroscopic methods (nuclear magnetic resonance and mass spectrometry).

Bioactivity-Guided Isolation of Antimicrobial and Antioxidant Metabolites from the Mushroom .

Bioassay-guided fractionation of the chloroform extract of led to the isolation of four secondary metabolites ⁻. Two of the compounds are lactones—osmundalactone () and 5-hydroxy-hex-2-en-4-olide ()—while and were identified as terphenyl quinones, spiromentins C and B, respectively. The structures of the compounds were established on the basis of NMR and MS spectroscopic analysis.