Experimental verification of halomethyl carbinol synthesis from carbonyl compounds using a TiCl-Mg bimetallic complex promoter.

A critical evaluation of the feasibility of a previously published method for synthesising halomethyl carbinols from carbonyl compounds and CHBr or CHCl using a bimetallic TiCl-Mg complex is presented. The synthesis of compounds lacking the -CH- group in their structure was achieved by following the procedures proposed in the reference literature or by introducing modifications to selected process parameters. These compounds were not identified as expected β-halohydrins but as products of reductive dimerisation or subsequent pinacolic rearrangement of carbonyl substrates.

The conjugates of 5'-deoxy-5-fluorocytidine and hydroxycinnamic acids - synthesis, anti-pancreatic cancer activity and molecular docking studies.

New amide conjugates 1-6 of hydroxycinnamic acids (HCA) and 5'-deoxy-5-fluorocytidine (5-dFCR), the prodrug of 5-fluorouracil (5-FU), were synthesized and tested against pancreatic cancer lines (PDAC). The compounds showed slightly higher efficacy against primary BxPC-3 cells (IC values of 14-45 μM) than against metastatic AsPC-1 (IC values of 37-133 μM), and similar to that of 5-FU for both PDAC lines. Compound 1, which has a -(acetyloxy)coumaroyl substituent, was found to be the most potent (IC = 14 μM) with a selectivity index of approximately 7 to normal dermal fibroblasts (IC = 96 μM).

The Conjugates of Indolo[2,3-]quinoline as Anti-Pancreatic Cancer Agents: Design, Synthesis, Molecular Docking and Biological Evaluations.

New amide conjugates of hydroxycinnamic acids (HCAs) and the known antineoplastic 5,11-dimethyl-5-indolo[2,3-]quinoline (DiMIQ), an analog of the natural alkaloid neocryptolepine, were synthesized and tested in vitro for anticancer activity. The compound 9-[((2-hydroxy)cinnamoyl)amino]-5,11-dimethyl-5-indolo[2,3-]quinoline (), which contains the ortho-coumaric acid fragment, demonstrated dose-dependent effectiveness against both normal BxPC-3 and metastatic AsPC-1 pancreatic cancer cells. The IC values for AsPC-1 and BxPC-3 were 336.

Efficient One-Pot Synthesis of Novel Caffeic Acid Derivatives as Potential Antimalarials.

New protocol for the preparation of the novel caffeic acid derivatives using the Wittig reaction has been applied to follow the principles of green chemistry. The compounds have been evaluated against chloroquine-sensitive and chloroquine-resistant strains. Their cytotoxicity to normal human dermal fibroblasts and their propensity to induce hemolysis have been also determined.

Lazarus Phenomenon or the Return from the Afterlife-What We Know about Auto Resuscitation.

Autoresuscitation is a phenomenon of the heart during which it can resume its spontaneous activity and generate circulation. It was described for the first time by K. Linko in 1982 as a recovery after discontinued cardiopulmonary resuscitation (CPR).

d-Glucose- and d-mannose-based antimetabolites. Part 4: Facile synthesis of mono- and di-acetates of 2-deoxy-d-glucose prodrugs as potentially useful antimetabolites.

2-Deoxy-d-glucose (2-DG), a compound known to interfere with d-glucose and d-mannose metabolism, has been tested as a potential anticancer and antiviral agent. Preclinical and clinical studies focused on 2-DG have highlighted several limitations related to 2-DG drug-like properties, such as poor pharmacokinetic properties. To overcome this problem, we proposed design and synthesis of novel 2-DG prodrugs that subsequently could be tested using a variety of biochemical and molecular methods.

The Use of the ICF Classification Sheet to Assess Cognitive-Behavioral Disorders and Verbal Communication in Patients after Ischemic and Hemorrhagic Stroke during Rehabilitation.

In patients after experiencing stroke, the cognitive-behavioral deficits and disorders of verbal communication limit the effectiveness of rehabilitation. The key is to diagnose them at an early stage of rehabilitation and to implement appropriate psychological and speech therapy. Identify differences in the frequency and effectiveness of cognitive-behavioral disorder therapy depending on the clinical type of stroke, assessed before and after rehabilitation treatment, and their presentation using the ICF (International Classification of Functioning, Disability, and Health) classification.

Antioxidant activity of novel diosgenin derivatives: Synthesis, biological evaluation, and in silico ADME prediction.

A series of novel diosgenin (DSG) derivatives has been synthesized and tested in vitro for their antioxidant activity. Initially, four analogues have been evaluated for their cytotoxicity using normal human skin fibroblast (NHDF) as model cells. As a result, 84% of NHDF cells were still alive at 5 µM, so these compounds can be considered as innoxious to fibroblasts at this concentration.

Structure-Activity Relationship of Hydroxycinnamic Acid Derivatives for Cooperating with Carnosic Acid and Calcitriol in Acute Myeloid Leukemia Cells.

Plant phenolic compounds have shown the ability to cooperate with one another at low doses in producing enhanced anticancer effects. This may overcome the limitations (e.g.

Unexpected Reaction Products of Uracil and Its Methyl Derivatives with Acetic Anhydride and Methylene Chloride.

New acetyl derivatives of uracil, 6-methyluracil, and thymine were obtained in the course of an unconventional synthesis in methylene chloride. It was shown that products with the acetyloxymethyl fragment are formed according to a mechanism different from that for products with the acetyloxyethyl group. In particular, for uracil it was proven that the reaction with AcO, TEA, and CHCl leads to 1-acetyloxymethyluracil, where the substituent is composed of the -CH- fragment that originated from CHCl and the 1-acetyloxy moiety from AcO.

Evaluation of the In Vitro Cytotoxic Activity of Caffeic Acid Derivatives and Liposomal Formulation against Pancreatic Cancer Cell Lines.

Pancreatic cancer belongs to the most aggressive group of cancers, with very poor prognosis. Therefore, there is an important need to find more potent drugs that could deliver an improved therapeutic approach. In the current study we searched for selective and effective caffeic acid derivatives.

Exploring the Participant-Related Determinants of Simulator Sickness in a Physical Motion Car Rollover Simulation as Measured by the Simulator Sickness Questionnaire.

Physical motion driving simulators serve as a valuable research and training tool. Since many simulator participants suffer from simulator sickness (SS), we aimed to gain a better understanding of participant-related variables that may influence its incidence and severity. The study involved a 2-min mobile-platform car rollover simulation conducted in a group of 100 healthy adult participants.

How paramedics perceive internal noise in ambulance? sensory processing sensitivity (SPS) and Subjective Noise Assessment.

Introduction: This article discusses the correlation between sensory processing sensitivity (SPS) as a feature of personality and temperament and paramedics' subjective perception of noise inside an ambulance. Description of the theoretical basis of SPS has been strongly depicted.

Materials And Methods: : Polish translation of SPS 12-item short scale and a survey concerning the subjective perception of noise inside an ambulance have been used in this research.

Synthesis of Thiol Derivatives of Biological Active Compounds for Nanotechnology Application.

An efficient method of thiol group introduction to the structure of common natural products and synthetic active compounds with recognized biological efficacy such genistein (), 5,11-dimethyl-5-indolo[2,3-b]quinolin (), capecitabine (), diosgenin (), tigogenin (), flumethasone (), fluticasone propionate (), ursolic acid methyl ester (), and β-sitosterol () was developed. In most cases, the desired compounds were obtained easily via two-step processes involving esterification reaction employing S-trityl protected thioacetic acid and the corresponding hydoxy-derivative, followed by removal of the trityl-protecting group to obtain the final compounds. The results of our preliminary experiments forced us to change the strategy in the case of genistein (), and the derivatization of diosgenin (), tigogenin (), and capecitabine () resulted in obtaining different compounds from those designed.

[Simulator sickness and the in Polish practice. A study involving professional drivers subject to compulsory initial and periodic qualification courses].

Background: A phenomenon of simulator sickness is measurable in terms of physiological symptoms. The article presents the practical use of the (SSQ) in post-exposure research, together with feedback given by the examined drivers.

Material And Methods: The study was conducted on the AutoSim AS 1600 simulator, and involved 130 drivers attending preliminary and periodic qualification courses in road transportation.

Synergistic Cytotoxicity of Methyl 4-Hydroxycinnamate and Carnosic Acid to Acute Myeloid Leukemia Cells Calcium-Dependent Apoptosis Induction.

Acute myeloid leukemia (AML) is a malignant hematopoietic disease with poor prognosis for most patients. Conventional chemotherapy has been the standard treatment approach for AML in the past 40 years with limited success. Although, several targeted drugs were recently approved, their long-term impact on survival of patients with AML is yet to be determined.

A diversity of alkylation/acylation products of uracil and its derivatives: synthesis and a structural study.

tert-Butyl dicarbonate (Boc2O) and ethyl iodide (EtI) reactions with uracil (U), thymine (T) and 6-methyluracil (6-MU) were performed following routine procedures in pyridine/DMF solvents and with DMAP as the catalyst. Among 20 synthesized compounds, a derivative of 6-methyluracil substituted by the Boc-pyridine moiety at the C5 position appeared unexpectedly. The NMR spectra confirmed the molecular structure of all uracil derivatives.

Design of Therapeutic Self-Assembled Monolayers of Thiolated Abiraterone.

The aim of our work was to synthetize of a new analogue of abiraterone-thiolated abiraterone (HS-AB) and design a gold surface monolayer, bearing in mind recent advances in tuning monolayer structures and using them as efficient drug delivery systems. Therapeutic self-assembled monolayers (TSAMs) were prepared by chemically attaching HS-AB to gold surfaces. Their properties were studied by voltammetry and atomic force microscopy (AFM).

Synthesis and Antioxidant Activity of Caffeic Acid Derivatives.

A series of caffeic acid derivatives were synthesized via a modified Wittig reaction which is a very important tool in organic chemistry for the construction of unsaturated carbon⁻carbon bonds. All reactions were performed in water medium at 90 °C. The aqueous Wittig reaction worked best when one unprotected hydroxyl group was present in the phenyl ring.

Efficient glycosylation of natural Danshensu and its enantiomer by sugar and 2-deoxy sugar donors.

An efficient methodology of the glycosylation process of a secondary plant metabolite (R-Danshensu) and its enantiomer by sugar and 2-deoxy sugar donors was developed. The overall synthesis of the new sugar derivatives involved two steps, starting from the previously synthesized protected R and S Danshensu (1 and 2). The deoxy sugar derivatives of R and S Danshensu were obtained from available tri-O-acetyl-2-deoxy-D-glucal and di-O-acetyl-2-deoxy-D-ramnal.

An efficient synthesis of indolo[2,3-b]quinoline guanidine derivatives with their in vitro and in vivo study.

An optimization of the guanidylation process by verifying the efficacy of common guanylation reagents in order to obtain the guanidine derivatives of indolo[2,3-b]quinoline has been performed. As a result, a high-yield procedure using ,'-di-Boc-''-triflylguanidine was applied to synthesize the guanidine derivative of indolo[2,3-b]quinoline in a gram scale for specific in vitro and in vivo biological research. Extensive studies on the antiproliferative activity against eight human tumor cell lines were completed.

Use of the hyphenated LC-MS/MS technique and NMR/IR spectroscopy for the identification of exemestane stress degradation products during the drug development.

Exemestane (6-Methyleneandrosta-1,4-diene-3,17-dione) active pharmaceutical ingredient (EE-3) was subjected to thermal, photolytic, oxidative, acidic and base stress conditions prescribed by the ICH (International Conference on Harmonization) guideline Q1A(R2). EE-3 was found to degrade in base, acidic and oxidative conditions. Eleven new degradation products of EE-3 were characterized by the LC-MS/MS technique.

Stressful Events and Serum Concentration of Substance P in Acne Patients.

Background: Psychological stress is an important factor of acne pathogenesis. Stress related production of hormones, cytokines and neuropeptides may result in the chronic course and exacerbations of the disease.

Objective: The aim of the study was to evaluate the relationship between acne severity, intensity of emotional stress and serum concentration of substance P (scSP), to compare the intensity of adversities, psychological stress and scSP in acne patients with healthy controls and to compare coping techniques for stress.