HPLC-based cytotoxicity profiling and LC-ESIQTOF-MS/MS analysis of Helichrysum leucocephalum.

Introduction: Helichrysum leucocephalum Boiss. (Asteraceae) is an endemic plant to Iran. No reports have studied the cytotoxicity of the plant. The current study aimed to evaluate the cytotoxicity of H. leucocephalum collected from Fars province (Iran) against MCF-7 and HDF cell lines using HPLC-based activity profiling and to annotate the active constituents by LC-ESIQTOF-MS/MS. Methods: H. leucocephalum was collected from three locations in Fars province. The dried flowers and leaves were separately extracted by percolation using methanol. The crude extracts were fractionated by liquid-liquid partitioning with dichloromethane (DCM) and aqueous methanol. The cytotoxicity of the fractions was evaluated against MCF-7 and HDF cells by Alamarblue assay. HPLC-based activity profiling was used to track the active constituents. LC-MS dereplication strategy was used for the annotation of the compounds in the active time window. LC-MS data were preprocessed by MZmine 3.3.0 and submitted to multivariate analysis to compare the differences and similarities in the metabolites of the samples. Results: The DCM fractions showed a dose-dependent cytotoxicity against the cancerous cells (IC50s, 9.8-105.1 µg/ml). In general, the metabolites of the flowers and their cytotoxicity were higher than the leaves. LCESIMS/MS analyses revealed that prenylated and geranylated α,ß-unsaturated spiroketal phloroglucinols were among the active constituents. Conclusion: It can be concluded that H. leucocephalum is a rich source of phloroglucinol derivatives with cytotoxic activities. Further phytochemical analysis is needed to characterize the bioactive components.

Comparative LC-ESIMS-Based Metabolite Profiling of Senna italica with Senna alexandrina and Evaluating Their Hepatotoxicity.

Senna Mill. (Fabaceae) is an important medicinal plant distributed worldwide. Senna alexandrina (S. alexandrina), the officinal species of the genus, is one of the most well-known herbal medicines traditionally used to treat constipation and digestive diseases. Senna italica (S. italica), another species of the genus, is native to an area ranging from Africa to the Indian subcontinent, including Iran. In Iran, this plant has been used traditionally as a laxative. However, very little phytochemical information and pharmacological reports investigating its safety of use are available. In the current study, we compared LC-ESIMS metabolite profiles of the methanol extract of S. italica with that of S. alexandrina and measured the content of sennosides A and B as the biomarkers in this genus. By this, we were able to examine the feasibility of using S. italica as a laxative agent like S. alexandrina. In addition, the hepatotoxicity of both species was evaluated against HepG2 cancer cell lines using HPLC-based activity profiling to localize the hepatotoxic components and evaluate their safety of use. Interestingly, the results showed that the phytochemical profiles of the plants were similar but with some differences, particularly in their relative contents. Glycosylated flavonoids, anthraquinones, dianthrones, benzochromenones, and benzophenones constituted the main components in both species. Nevertheless, some differences, particularly in the relative amount of some compounds, were observed. According to the LC-MS results, the amounts of sennoside A in S. alexandrina and S. italica were 1.85 ± 0.095% and 1.00 ± 0.38%, respectively. Moreover, the amounts of sennoside B in S. alexandrina and S. italica were 0.41 ± 0.12 % and 0.32 ± 0.17%, respectively. Furthermore, although both extracts showed significant hepatotoxicity at concentrations of 50 and 100 µg/mL, they were almost non-toxic at lower concentrations. Taken together, according to the results, the metabolite profiles of S. italica and S. alexandrina showed many compounds in common. However, further phytochemical, pharmacological, and clinical studies are necessary to examine the efficacy and safety of S. italica as a laxative agent.

Chemophobia and passion: why chemists should desire Marcel Proust.

In this article, we introduce a new communication strategy called the "communication success dimension" for the suppression and eradication of chemophobia. We explain, using recent examples, that chemophobia presents a danger not only to the science of chemistry but also to humankind. Based on the latest insights from communication research, we emphasize the need to bring more passion, dedication, and human factors into the communication of chemistry. We demonstrate the application of this new strategy by employing Marcel Proust's In Search of Lost Time to combat chemophobia.

Non-enzymatic electrochemical determination of cholesterol in dairy products on boron-doped diamond electrode.

Determination of cholesterol in food matrices is essential for quality control concerning the health of consumers. Herein, a simple electrochemical approach for cholesterol quantitation in dairy products is evaluated. The newly developed differential pulse voltammetric method using acetonitrile-perchloric acid mixture as a supporting electrolyte is statistically compared to GC-MS and HPLC-UV. Oxidation signals of cholesterol at +1.5 V and +1.4 V (vs. Ag/AgNO3 in acetonitrile) provide detection limits of 4.9 µM and 6.1 µM on boron-doped diamond and glassy carbon electrodes, respectively. A simple liquid-liquid extraction procedure from dairy products into hexane resulted in a recovery rate of (74.8 ± 3.8)%. The method provides results in close agreement (at a 95% confidence level) with GC-MS, while HPLC-UV resulted in a significant difference in estimated cholesterol concentrations for all samples. This newly developed method is a simpler, faster and cheaper alternative to instrumentally demanding MS-based methods and clearly outperforms HPLC-UV.

QSAR based on hybrid optimal descriptors as a tool to predict antibacterial activity against Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus bacterial infections are still a serious health care problem. Therefore, the development of new drugs for these infections is a constant requirement. Quantitative structure-activity relationship (QSAR) methods can assist this development. METHODS: The study included 151 structurally diverse compounds with antibacterial activity against S. aureus ATCC 25923 (Endpoint 1) or the drug-resistant clinical isolate of S. aureus (Endpoint 2). QSARs based on hybrid optimal descriptors were used. RESULTS: The predictive potential of developed models has been checked with three random splits into training, passive training, calibration, and validation sets. The proposed models give satisfactory predictive models for both endpoints examined. CONCLUSIONS: The results of the study show the possibility of SMILES-based QSAR in the evaluation of the antibacterial activity of structurally diverse compounds for both endpoints. Although the developed models give satisfactory predictive models for both endpoints examined, splitting has an apparent influence on the statistical quality of the models.

Chemophobia cured by chemists: chemists as children of the Sun.

The success of chemists in the fight against COVID-19 provides us with a unique opportunity for strengthening the position of chemistry in society and suppressing chemophobia which has badly affected the image and development of chemistry over several decades. By highlighting the unique merits of chemistry in controlling infections and healing diseases, we propose developing a communication strategy "Chemists as children of the Sun". The time is ripe for chemists to take control of the story of chemistry. We believe that chemists must help the public to see chemistry in a whole new light. Only a positive perception of chemistry and the chemical profession will secure a sufficient supply of new talents, ideas, and also financial resources for the development of this unique and irreplaceable science for humanity.

Chemophobia versus the identity of chemists: heroes of chemistry as an effective communication strategy.

ABSTRACT: Decades of chemophobia are taking a high toll on chemistry. As current surveys suggest, people are displaying an irrational desire to live in a world without chemistry, but at the same time are unable to answer trivial chemistry questions. Constant questioning of the importance of chemistry induced by chemophobia leads to a weakening of the identity of chemists and can have negative consequences on the reproduction of chemistry. The need for the support of a positive perception of the chemical profession and an offer of positive examples for self-identification is the result. Everyday communication thus becomes the background on which the determination of the identity of the chemist takes place. The new communication strategy, which we call "heroes of chemistry", aims not only to add a much-needed human touch to chemistry communications, but also to create the conditions for strengthening the identity of the chemist.

A novel voltammetric approach to the detection of primary bile acids in serum samples.

An innovative voltammetric approach to the detection of cholic and chenodeoxycholic acids is presented. These two primary bile acids are important biomarkers of liver function in humans and are involved in many physiological processes in the human body. Herein we describe a way to reproducibly convert the hard-to-detect bile acid molecule into an easily detectable derivative in situ using 0.1 M HClO4 in acetonitrile (water content 0.55%). Under these conditions the bile acids are dehydrated and the resulting alkenes can be subsequently oxidized electrochemically on polished boron-doped diamond electrode under unchanged conditions at approximately +1.2 V vs. Ag/AgNO3 in acetonitrile. After optimization, differential pulse voltammetry provides competitive limits of detection of 0.5 µM and 1.0 µM for cholic and chenodeoxycholic acid, respectively, with a linear course of calibration dependency to the minimum of 80 µM. The method was applied for detection of cholic and chenodeoxycholic acids in artificial and human serum samples using single solid phase extraction on C-18 cartridge for preliminary separation of the analytes. High recoveries of 80-90% were consistently obtained by the proposed voltammetric method and reference HPLC with fluorescence detection for human serum samples, confirming good selectivity for real-life samples.

Medicinal Chemistry Meets Electrochemistry: Redox Potential in the Role of Endpoint or Molecular Descriptor in QSAR/QSPR.

Many biochemical reactions are based on redox reactions. Therefore, the redox potential of a chemical compound may be related to its therapeutic or physiological effects. The study of redox properties of compounds is a domain of electrochemistry. The subject of this review is the relationship between electrochemistry and medicinal chemistry, with a focus on quantifying these relationships. A summary of the relevant achievements in the correlation between redox potential and structure, therapeutic activity, resp., is presented. The first part of the review examines the applicability of QSPR for the prediction of redox properties of medically important compounds. The second part brings the exhaustive review of publications using redox potential as a molecular descriptor in QSAR of biological activity. Despite the complexity of medicinal chemistry and biological reactions, it is possible to employ redox potential in QSAR/QSPR. In many cases, this electrochemical parameter plays an essential but rarely absolute role.

Pharmacists among Members of the Czech-Moravian Capuchin Province.

Based on a profound examination and evaluation of archival materials, the paper reconstructs the lives of eighteen pharmacists - members of the Czech-Moravian Capuchin Province from the 17th to the 19th century, of which sixteen served as monastic pharmacists. In addition to the identified biographical data (based on archival materials), the Latin summary reports on the life of a particular capuchin on the occasion of his death (the so-called elogia) from the Capuchin Provincial Chronicle (Annales capucinorum) are edited, together with their commented Czech translation. The discovered data allow a deeper insight into the pharmaceutical history of the Czech-Moravian Capuchin Province, where three monastic pharmacies were operated in Brno, Prague in Hradčany and Olomouc, and also a monastic pharmaceutical study was established. The published material also provides some new data on contemporary pharmaceutical practice, which are set in the context of literature. The paper illustrates the transfer of knowledge between the world of secular and monastic pharmacy at the places where future monastic pharmacists received their education (the pharmacies “The White Eagle” in Karlovy Vary, the pharmacy of brothers hospitallers in Prostějov, “The Golden Eagle” in Opava, “The White Unicorn” in the Old Town of Prague). The paper also highlights the intensive involvement of monastic pharmacists in the management of plague epidemics in the years 1680-1713 (often at the cost of their own lives), as well as the above-standard proximity to the patients in monastic hospitals in carrying out routine nursing and pharmacy practice. The paper adds sharper contours to the image of the pharmacist at that time by detailing the life stories of individual pharmacists (e.g., the previous career as a military surgeon and the iconographic circumstances of death, or the career extension in the form of participation in the order meetings in Rome). Analysis of the preserved manuscript Annotationes medicae Fr. Absolonis from the turn of the 18th and 19th centuries not only introduces an interesting pharmaceutical memorabilia, but also illustrates the professional maturation of the last Capuchin pharmacist. In the final part of the paper, the data about twenty-two pharmacists who unsuccessfully tried to join the Capuchin Order are given. It not only demonstrates admission practice in the Capuchin order, in which spiritual interest outweighed the practical, but also bears witness to other pharmaceutical phenomena of the time, such as the fate of the pharmacist from the abolished Jesuit Order or the development of pharmacy in the Carthusian monastery in Valdice.

Pharmacy and Johann Wolfgang von Goethe: Pharmacists as Goethes chemistry teaches.

At the turn of the 18th and 19th centuries, when pharmacy was established as a modern scientific discipline, pharmacists played an important role in spreading the latest discoveries in the field of chemistry, being virtually the only established representatives of the field. The article focuses on a mutually enriching dialogue between the prominent personality of the time - the poet, writer and statesman, as well as the scientist - Johann Wolfgang von Goethe and the major representatives of the pharmacy of that time, especially J. R. Spielmann, W. H. Buchholz, J. F. Göttling, and J. W. Döbereiner. Goethe, who has been deeply interested in chemistry all over his life, has found his teachers of chemistry and co-workers in this field among the pharmacists and, in return, has provided them with an extraordinary support for the realization of their scientific and professional interests. This cooperation is illustrated by the solution of the mysterious method of poisoning described in the ancient literature, on which the poet collaborated with J. W. Döbereiner. Attention is also paid to the reflection of pharmacy in Goethe's work (Hermann und Dorothea, Faust). The poet's numerous stays in Bohemia, where he spent more than three years of his life, naturally brought him into contact with a number of pharmacists of the Czech Kingdom.

Non-Enzymatic Electrochemistry in Characterization and Analysis of Steroid Compounds.

This review summarizes achievements in electrochemistry-related research of steroid-based compounds in clinical, pharmaceutical, and environmental analysis. Special attention is paid to compounds possessing none or only isolated double bonds at the steroid core. Their direct redox activity is limited to far positive/negative potentials under variety of conditions and electrode materials and relies on the functional groups attached to the steroid skeleton, or as the case may be its double bond or moieties present at the side chain. The possibilities of electroanalytical methods in sterol characterization and analysis are demonstrated in a table with 31 references devoted to direct voltammetric and amperometric methods of oxidation of cholesterol, phytosterols, oxysterols, and related compounds at carbon-based and metal-based nanoparticles modified electrodes, and the reduction of bile acids and their conjugates at mercury-based electrodes, and modified glassy carbon electrodes. Furthermore, methods based on the indirect oxidation of cholesterol using bromine species as a mediator at platinum electrode and non-enzymatic cholesterol biosensors are reviewed. Their drawbacks and benefits are discussed with respect to the challenging task of identification and quantitation of these compounds in biological matrices, otherwise mostly performed using expensive mass spectrometric techniques preceded by a chromatographic separation step.

Electrokinetic injection of samples into a short electrophoretic capillary controlled by piezoelectric micropumps.

Electrokinetic sample injection using two piezoelectric micropumps has been proposed for electrophoresis in short capillaries. The sample is brought to the injection end of the capillary using one of them. Then, the high-voltage source is turned on and the sample is injected electrokinetically for a defined time. The injection is terminated by removal of the sample zone by the flowing separation electrolyte pumped by the second piezoelectric micropump. The RSD value, expressing the repeatability of the injection, does not exceed 4%. The injection apparatus does not contain any mobile mechanical components, there is no movement of the capillary and both its ends remain constantly in the solution during both the sample injection and separation. Thus, the micropumps replace the six-way injection valve and linear pump in similar types of injection apparatuses. The injection was tested in the separation and determination of ammonium and potassium ions in two samples of mineral fertilizers. The separation was performed in background electrolyte containing 500 mM of acetic acid + 20 mM Tris + 2 mM 18-crown-6 (pH 3.3) in a capillary with id 50 µm and total length/length to the contactless conductivity detector of 10.5/8 cm. The injection and separation took place at a voltage of 5 kV and the separation time equaled 20 s. The measured values of the analyte contents corresponded to the value declared by the manufacturer within the reliability interval, where RSD equaled between 3.5 and 4.7%.

Prediction of retention characteristics of heterocyclic compounds.

The CORAL software ( http://www.insilico.eu/coral ) was used to build up quantitative structure-property relationships (QSPRs) for the retention characteristics of 93 derivatives of three groups of heterocyclic compounds: 2-phenyl-1,3-benzoxazoles, 4-benzylsulfanylpyridines, and benzoxazines. The QSPRs are one-variable models based on the optimal descriptors calculated from the molecular structure represented by simplified molecular input-line entry systems (SMILES). Each symbol (or two undivided symbols) of SMILES is characterized by correlation weight. The optimal descriptor is the sum of the correlation weights. The numerical data on the correlation weights were calculated with the Monte Carlo method by the manner which provides best correlation between endpoint and optimal descriptor for the calibration set. The predictive ability of the model is checked with the validation set (compounds invisible during building up of the model). The approach has been checked with three random splits into the training, calibration, and validation sets: all models have apparent predictive potential. The mechanistic interpretation of the molecular features extracted from SMILES as the promoters of increase or decrease of examined endpoints is suggested.

[Pharmaceutical History of the Capuchin Monastery in Prague-Hradcany Part I. Monastic Pharmacy]. / Farmaceutická historie kapucínského klástera v Praze na Hradcanech Cást I. Klásterní lékárna.

Based on a profound examination and thorough evaluation of archival materials and preserved equipment, the article provides a unique perspective on the unknown history of pharmacy at the capuchin monastery in Prague-Hradcany. The intramural pharmacy was established around the year 1680, and was practised to 1822. The article identifies the capuchin pharmacists and their line of succession. Pharmaceutical literature from the monastic library is listed and described, including rare manuscripts. The preserved high baroque equipment of the pharmacy is described in detail, and an iconography analysis of the hidden meaning of its unique decoration is offered.Key words: pharmaceutical history capuchins monastic pharmacies baroque.

[Pharmaceutical history of capuchin monastery in Prague-Hradcan Part II. Capuchin balsam (Balsamum capucinorum)]. / Farmaceutická historie kapucínského klástera v Praze na Hradcanech Cást II. Kapucínský balzám (Balsamum capucinorum).

The history of traditional capuchin balsam is the focal point of the second part of the article on the unknown history of pharmacy at the capuchin monastery in Prague-Hradcany. Capuchin balsam, a medicinal speciality, was being manufactured in the monastery from the end of the 18th century till the year 1950. It is a spirit tincture, its prescription originating from the formulation by Oswald Croll. Balsamum Peruvianum, Gummiresina myrrha, Gummiresina olibanum, and Styrax are the main ingredients, besides assorted plants. The balsam was taken as an antiseptic, antiphlogistic, and analgesic. The balsam was a favoured rustic medicine, and it was sold also abroad (Germany, Poland, USA, Ireland, Belgium). The profit made from the sale of the balsam supported the reconstruction and the maintenance of the monastery and the local theological studies. Other medical formulations connected with the name of the capuchin order are also mentioned.Key words: pharmaceutical history capuchins capuchin balsam monastics pharmacies.

The Monte Carlo method based on eclectic data as an efficient tool for predictions of endpoints for nanomaterials - two examples of application.

The theoretical predictions of endpoints related to nanomaterials are attractive and more efficient alternatives for their experimental determinations. Such type of calculations for the "usual" substances (i.e. non nanomaterials) can be carried out with molecular graphs. However, in the case of nanomaterials, descriptors traditionally used for the quantitative structure--property/activity relationships (QSPRs/QSARs) do not provide reliable results since the molecular structure of nanomaterials, as a rule, cannot be expressed by the molecular graph. Innovative principles of computational prediction of endpoints related to nanomaterials extracted from available eclectic data (technological attributes, conditions of the synthesis, etc.) are suggested, applied to two different sets of data, and discussed in this work.

SMILES-based quantitative structure-property relationships for half-wave potential of N-benzylsalicylthioamides.

Optimal descriptors calculated with Simplified Molecular Input Line Entry System (SMILES) notation have been used in quantitative structure-property relationships (QSPR) of half-wave potential of N-benzylsalicylthioamides. The QSPR developed is one-variable model based on the optimal descriptors calculated with the Monte Carlo method. The approach has been checked up with three random splits into the training and test sets. Mechanistic interpretations (structural alerts related to the half-wave potential) of the model are discussed.

QSPR modeling of the half-wave potentials of benzoxazines by optimal descriptors calculated with the SMILES.

Optimal descriptors calculated with Simplified Molecular Input Line Entry System (SMILES) notation have been used in quantitative structure-property relationships (QSPR) modeling electrochemical half-wave potential of benzoxazine derivatives by one-variable correlations.