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Medicinal Chemistry in Europe III

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 38297

Special Issue Editors


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Guest Editor
Institute of Neurophysiopathology (INP), Aix-Marseille University, Faculté des sciences médicales et paramédicales, 27, Bd Jean Moulin, 13005 Marseille, France
Interests: antimicrobial peptides; antibacterial; antibiotics; structure-activity relationships; bacteriocins; drug design; peptide engineering
Special Issues, Collections and Topics in MDPI journals

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Co-Guest Editor
LR Biotechnology and Bio-Geo Resources Valorization (LR11ES31), Higher Institute for Biotechnology, University of Manouba, Sidi Thabet, Tunisia
Interests: metabolomics; biomarkers; microbiota; cancer

Special Issue Information

Dear Colleagues,

This Special Issue on “Medicinal Chemistry in Europe III” of the journal Molecules deals with the structure–activity relationship of all the natural molecules of interest in a wide range of areas (microbiology, neurobiology, pharmacology, immunology, cancerology, toxicology, etc.), from basic research to more applied clinical developments. Studies on molecules of a varied nature (i.e., peptides/proteins and organic compounds), size, and functions—as well as molecular complexes—will be considered for publication in the Special Issue. Submissions of manuscripts in the various fields of research and from all over the world are strongly encouraged.

Dr. Jean-Marc Sabatier
Prof. Dr. Soumaya Kouidhi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Natural molecules
  • Organic compounds
  • Peptides
  • Proteins
  • Carbohydrates
  • Lipids
  • Glycopeptides/glycoproteins
  • Lipopeptides/lipoproteins
  • Structure–function

Published Papers (14 papers)

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Research

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10 pages, 3338 KiB  
Article
Fast and Noninvasive Hair Test for Preliminary Diagnosis of Mood Disorders
by Magdalena Świądro-Piętoń, Kai A. Morawiec, Anna Wójtowicz, Sara Świądro, Rafał Kurczab, Dominika Dudek and Renata Wietecha-Posłuszny
Molecules 2022, 27(16), 5318; https://doi.org/10.3390/molecules27165318 - 20 Aug 2022
Cited by 2 | Viewed by 1636
Abstract
The main objective of this study was to develop a test for the fast and noninvasive prediagnosis of mood disorders based on the noninvasive analysis of hair samples. The database included 75 control subjects (who were not diagnosed with depression) and 40 patients [...] Read more.
The main objective of this study was to develop a test for the fast and noninvasive prediagnosis of mood disorders based on the noninvasive analysis of hair samples. The database included 75 control subjects (who were not diagnosed with depression) and 40 patients diagnosed with mood disorders such as depression or bipolar disorder. Both women and men, aged 18–65 years, participated in the research. After taking the hair samples, they were washed (methanol–water–methanol by shaking in a centrifuge for two min) and air-dried in a fume hood. Each hair collection was analyzed using Fourier transform infrared spectroscopy attenuated total reflection (ATR-FTIR) spectroscopy. Subsequently, the results obtained were analyzed based on chemometric methods: hierarchical cluster analysis (HCA) and principal component analysis (PCA). As a results of the research conducted, potential differences were noticed. There was a visible change in the spectra intensity at around 2800–3100 cm−1 and smaller differences around 1460 cm−1; the bands can be assigned to protein vibrations. However, these are preliminary studies that provide a good basis for the development of a test for the initial diagnosis of mood disorders. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Europe III)
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23 pages, 2280 KiB  
Article
Screening an In-House Isoquinoline Alkaloids Library for New Blockers of Voltage-Gated Na+ Channels Using Voltage Sensor Fluorescent Probes: Hits and Biases
by Quentin Coquerel, Claire Legendre, Jacinthe Frangieh, Stephan De Waard, Jérôme Montnach, Leos Cmarko, Joseph Khoury, Charifat Said Hassane, Dimitri Bréard, Benjamin Siegler, Ziad Fajloun, Harold De Pomyers, Kamel Mabrouk, Norbert Weiss, Daniel Henrion, Pascal Richomme, César Mattei, Michel De Waard, Anne-Marie Le Ray and Christian Legros
Molecules 2022, 27(13), 4133; https://doi.org/10.3390/molecules27134133 - 28 Jun 2022
Cited by 2 | Viewed by 2427
Abstract
Voltage-gated Na+ (NaV) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel NaV channel ligands. With the objective of discovering new blockers of NaV channel ligands, we screened [...] Read more.
Voltage-gated Na+ (NaV) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel NaV channel ligands. With the objective of discovering new blockers of NaV channel ligands, we screened an In-House vegetal alkaloid library using fluorescence cell-based assays. We screened 62 isoquinoline alkaloids (IA) for their ability to decrease the FRET signal of voltage sensor probes (VSP), which were induced by the activation of NaV channels with batrachotoxin (BTX) in GH3b6 cells. This led to the selection of five IA: liriodenine, oxostephanine, thalmiculine, protopine, and bebeerine, inhibiting the BTX-induced VSP signal with micromolar IC50. These five alkaloids were then assayed using the Na+ fluorescent probe ANG-2 and the patch-clamp technique. Only oxostephanine and liriodenine were able to inhibit the BTX-induced ANG-2 signal in HEK293-hNaV1.3 cells. Indeed, liriodenine and oxostephanine decreased the effects of BTX on Na+ currents elicited by the hNaV1.3 channel, suggesting that conformation change induced by BTX binding could induce a bias in fluorescent assays. However, among the five IA selected in the VSP assay, only bebeerine exhibited strong inhibitory effects against Na+ currents elicited by the hNav1.2 and hNav1.6 channels, with IC50 values below 10 µM. So far, bebeerine is the first BBIQ to have been reported to block NaV channels, with promising therapeutical applications. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Europe III)
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12 pages, 1903 KiB  
Article
The DI-SPME Method for Determination of Selected Narcotics and Their Metabolites, and Application to Bone Marrow and Whole Blood Analysis
by Magdalena Świądro-Piętoń, Alicja Chromiec, Marcin Zawadzki and Renata Wietecha-Posłuszny
Molecules 2022, 27(13), 4116; https://doi.org/10.3390/molecules27134116 - 27 Jun 2022
Cited by 3 | Viewed by 1733
Abstract
The present investigation utilised the quick and easy SPME/LC-MS method to determine selected narcotic substances and their metabolites in whole blood. The study included qualitative analysis and validation of the method. Analytes were determined in the linearity range of 25–300 ng/mL. The precision [...] Read more.
The present investigation utilised the quick and easy SPME/LC-MS method to determine selected narcotic substances and their metabolites in whole blood. The study included qualitative analysis and validation of the method. Analytes were determined in the linearity range of 25–300 ng/mL. The precision during and between days (in general CV < 13.41%), and the LOD which results in between 0.36 and 11.08 ng/mL, and the LOQ between 1.20 and 36.90 ng/mL were investigated. The validation results obtained, as well as the results of subsequent in-laboratory tests, confirmed the applicability of the method in the analysis of blood samples. An attempt to apply the method to the analysis of bone marrow samples has yielded promising results; however, more detailed studies are needed in this area. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Europe III)
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18 pages, 4742 KiB  
Article
Synthesis and Structural Study of Amidrazone Derived Pyrrole-2,5-Dione Derivatives: Potential Anti-Inflammatory Agents
by Renata Paprocka, Leszek Pazderski, Liliana Mazur, Małgorzata Wiese-Szadkowska, Jolanta Kutkowska, Michalina Nowak and Anna Helmin-Basa
Molecules 2022, 27(9), 2891; https://doi.org/10.3390/molecules27092891 - 30 Apr 2022
Cited by 10 | Viewed by 2271
Abstract
1H-pyrrole-2,5-dione derivatives are known for their wide range of pharmacological properties, including anti-inflammatory and antimicrobial activities. This study aimed to synthesize new 3,4-dimethyl-1H-pyrrole-2,5-dione derivatives 2a2f in the reaction of N3-substituted amidrazones with 2,3-dimethylmaleic anhydride and [...] Read more.
1H-pyrrole-2,5-dione derivatives are known for their wide range of pharmacological properties, including anti-inflammatory and antimicrobial activities. This study aimed to synthesize new 3,4-dimethyl-1H-pyrrole-2,5-dione derivatives 2a2f in the reaction of N3-substituted amidrazones with 2,3-dimethylmaleic anhydride and evaluate their structural and biological properties. Compounds 2a2f were studied by the 1H-13C NMR two-dimensional techniques (HMQC, HMBC) and single-crystal X-ray diffraction (derivatives 2a and 2d). The anti-inflammatory activity of compounds 2a2f was examined by both an anti-proliferative study and a production study on the inhibition of pro-inflammatory cytokines (IL-6 and TNF-α) in anti-CD3 antibody- or lipopolysaccharide-stimulated human peripheral blood mononuclear cell (PBMC) cultures. The antibacterial activity of compounds 2a–2f against Staphylococcus aureus, Enterococcus faecalis, Micrococcus luteus, Esherichia coli, Pseudomonas aeruginosa, Yersinia enterocolitica, Mycobacterium smegmatis and Nocardia corralina strains was determined using the broth microdilution method. Structural studies of 2a2f revealed the presence of distinct Z and E stereoisomers in the solid state and the solution. All compounds significantly inhibited the proliferation of PBMCs in anti-CD3-stimulated cultures. The strongest effect was observed for derivatives 2a2d. The strongest inhibition of pro-inflammatory cytokine production was observed for the most promising anti-inflammatory compound 2a. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Europe III)
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23 pages, 3317 KiB  
Article
Antimicrobial Activity and DFT Studies of a Novel Set of Spiropyrrolidines Tethered with Thiochroman-4-one/Chroman-4-one Scaffolds
by Nourhène Chouchène, Amani Toumi, Sarra Boudriga, Hayet Edziri, Mansour Sobeh, Mohamed A. O. Abdelfattah, Moheddine Askri, Michael Knorr, Carsten Strohmann, Lukas Brieger and Armand Soldera
Molecules 2022, 27(3), 582; https://doi.org/10.3390/molecules27030582 - 18 Jan 2022
Cited by 20 | Viewed by 2434
Abstract
A novel series of 14 spiropyrrolidines bearing thiochroman-4-one/chroman-4-one, and oxindole/acenaphthylene-1,2-dione moieties were synthesized and characterized by spectroscopic techniques, as well as by three X-ray diffraction studies, corroborating the stereochemistry. Quantum chemical calculations studies, using the DFT approach, were performed to rationalize the stereochemical [...] Read more.
A novel series of 14 spiropyrrolidines bearing thiochroman-4-one/chroman-4-one, and oxindole/acenaphthylene-1,2-dione moieties were synthesized and characterized by spectroscopic techniques, as well as by three X-ray diffraction studies, corroborating the stereochemistry. Quantum chemical calculations studies, using the DFT approach, were performed to rationalize the stereochemical outcome. These N-heterocycles were evaluated for their antibacterial and antifungal activities against some pathogenic organisms. Several compounds displayed moderate to excellent activity towards the screened microbe strains in the study compared to Amoxicillin (AMX), Ampicillin (AMP), and Amphotericin B. Furthermore, a structural activity relationship (SAR) was established considering the synthesized compounds. Pharmacokinetic studies reveal that these derivatives exhibit an acceptable predictive ADMET profile (Absorption, Distribution, Metabolism, Excretion and Toxicity) and good drug-likeness. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Europe III)
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10 pages, 1913 KiB  
Article
Copper and Zinc as Potential Biomarkers of Mood Disorders and Pandemic Syndrome
by Magdalena Świądro, Klaudia Ordon, Małgorzata Herman, Dominika Dudek and Renata Wietecha-Posłuszny
Molecules 2022, 27(1), 91; https://doi.org/10.3390/molecules27010091 - 24 Dec 2021
Cited by 5 | Viewed by 2972
Abstract
The diagnosis of affective disorders has been the subject of constant research by clinicians from all over the world for many years. Making an appropriate diagnosis among patients suffering from mood disorders is sometimes problematic due to the personality-changing nature of patients and [...] Read more.
The diagnosis of affective disorders has been the subject of constant research by clinicians from all over the world for many years. Making an appropriate diagnosis among patients suffering from mood disorders is sometimes problematic due to the personality-changing nature of patients and the similarity in the clinical picture of episodes in affective disorders. For this reason, there is a need to develop rapid and effective methods of determining biological markers that differentiate these diseases. The research was carried out with blood taken from 15 patients and 15 volunteers. The analysis of biological material for trace concentrations of zinc and copper was carried out with the use of ultrasensitive triple-quadrupole inductively coupled plasma mass spectrometry (TQ ICP-MS). The obtained results prove that the concentration of copper in the test group was lower than in the control group. For the zinc concentrations, the inverse relationship was observed. The group of patients was characterized by a higher concentration of this element than the group of healthy volunteers. Summarizing the obtained results and comparing them with the results of studies by other authors, it was found that zinc and copper may be potential biomarkers of affective disorders and pandemic syndrome. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Europe III)
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12 pages, 12823 KiB  
Article
Towards an Improvement of Anticancer Activity of Benzyl Adenosine Analogs
by Verdiana Covelli, Manuela Grimaldi, Rosario Randino, Mohammad Firoznezhad, Maria Chiara Proto, Veronica De Simone, Gianluca Matteoli, Patrizia Gazzerro, Maurizio Bifulco, Anna Maria D’Ursi and Manuela Rodriquez
Molecules 2021, 26(23), 7146; https://doi.org/10.3390/molecules26237146 - 25 Nov 2021
Cited by 1 | Viewed by 1839
Abstract
N6-Isopentenyladenosine (i6A) is a naturally occurring modified nucleoside displaying in vitro and in vivo antiproliferative and pro-apoptotic properties. In our previous studies, including an in silico inverse virtual screening, NMR experiments and in vitro enzymatic assays, we demonstrated that i6A targeted [...] Read more.
N6-Isopentenyladenosine (i6A) is a naturally occurring modified nucleoside displaying in vitro and in vivo antiproliferative and pro-apoptotic properties. In our previous studies, including an in silico inverse virtual screening, NMR experiments and in vitro enzymatic assays, we demonstrated that i6A targeted farnesyl pyrophosphate synthase (FPPS), a key enzyme involved in the mevalonate (MVA) pathway and prenylation of downstream proteins, which are aberrant in several cancers. Following our interest in the anticancer effects of FPPS inhibition, we developed a panel of i6A derivatives bearing bulky aromatic moieties in the N6 position of adenosine. With the aim of clarifying molecular action of N6-benzyladenosine analogs on the FPPS enzyme inhibition and cellular toxicity and proliferation, herein we report the evaluation of the N6-benzyladenosine derivatives’ (compounds 2a–m) effects on cell viability and proliferation on HCT116, DLD-1 (human) and MC38 (murine) colorectal cancer cells (CRC). We found that compounds 2, 2a and 2c showed a persistent antiproliferative effect on human CRC lines and compound 2f exerted a significant effect in impairing the prenylation of RAS and Rap-1A proteins, confirming that the antitumor activity of 2f was related to the ability to inhibit FPPS activity. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Europe III)
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17 pages, 3004 KiB  
Article
Polyamines Upregulate Cephalosporin C Production and Expression of β-Lactam Biosynthetic Genes in High-Yielding Acremonium chrysogenum Strain
by Alexander A. Zhgun and Mikhail A. Eldarov
Molecules 2021, 26(21), 6636; https://doi.org/10.3390/molecules26216636 - 2 Nov 2021
Cited by 10 | Viewed by 2248
Abstract
The high-yielding production of pharmaceutically significant secondary metabolites in filamentous fungi is obtained by random mutagenesis; such changes may be associated with shifts in the metabolism of polyamines. We have previously shown that, in the Acremonium chrysogenum cephalosporin C high-yielding strain (HY), the [...] Read more.
The high-yielding production of pharmaceutically significant secondary metabolites in filamentous fungi is obtained by random mutagenesis; such changes may be associated with shifts in the metabolism of polyamines. We have previously shown that, in the Acremonium chrysogenum cephalosporin C high-yielding strain (HY), the content of endogenous polyamines increased by four- to five-fold. Other studies have shown that the addition of exogenous polyamines can increase the production of target secondary metabolites in highly active fungal producers, in particular, increase the biosynthesis of β-lactams in the Penicillium chrysogenum Wis 54–1255 strain, an improved producer of penicillin G. In the current study, we demonstrate that the introduction of exogenous polyamines, such as spermidine or 1,3-diaminopropane, to A. chrysogenum wild-type (WT) and HY strains, leads to an increase in colony germination and morphological changes in a complete agar medium. The addition of 5 mM polyamines during fermentation increases the production of cephalosporin C in the A. chrysogenum HY strain by 15–20% and upregulates genes belonging to the beta-lactam biosynthetic cluster. The data obtained indicate the intersection of the metabolisms of polyamines and beta-lactams in A. chrysogenum and are important for the construction of improved producers of secondary metabolites in filamentous fungi. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Europe III)
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15 pages, 5538 KiB  
Article
A Facile Approach to Bis(isoxazoles), Promising Ligands of the AMPA Receptor
by Dmitry A. Vasilenko, Kirill S. Sadovnikov, Kseniya N. Sedenkova, Dmitry S. Karlov, Eugene V. Radchenko, Yuri K. Grishin, Victor B. Rybakov, Tamara S. Kuznetsova, Vladimir L. Zamoyski, Vladimir V. Grigoriev, Vladimir A. Palyulin and Elena B. Averina
Molecules 2021, 26(21), 6411; https://doi.org/10.3390/molecules26216411 - 23 Oct 2021
Cited by 11 | Viewed by 2018
Abstract
A convenient synthetic approach to novel functionalized bis(isoxazoles), the promising bivalent ligands of the AMPA receptor, was elaborated. It was based on the heterocyclization reactions of readily available electrophilic alkenes with the tetranitromethane-triethylamine complex. The structural diversity of the synthesized compounds was demonstrated. [...] Read more.
A convenient synthetic approach to novel functionalized bis(isoxazoles), the promising bivalent ligands of the AMPA receptor, was elaborated. It was based on the heterocyclization reactions of readily available electrophilic alkenes with the tetranitromethane-triethylamine complex. The structural diversity of the synthesized compounds was demonstrated. In the electrophysiological experiments using the patch clamp technique on Purkinje neurons, the compound 1,4-phenylenedi(methylene)bis(5-aminoisoxazole-3-carboxylate) was shown to be highly potent positive modulator of the AMPA receptor, potentiating kainate-induced currents up to 70% at 10−11 M. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Europe III)
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19 pages, 4251 KiB  
Article
Peptaibol-Containing Extracts of Trichoderma atroviride and the Fight against Resistant Microorganisms and Cancer Cells
by Ján Víglaš, Simona Dobiasová, Jitka Viktorová, Tomáš Ruml, Vanda Repiská, Petra Olejníková and Helena Gbelcová
Molecules 2021, 26(19), 6025; https://doi.org/10.3390/molecules26196025 - 4 Oct 2021
Cited by 10 | Viewed by 2137
Abstract
Fighting resistance to antibiotics and chemotherapeutics has brought bioactive peptides to the fore. Peptaibols are short α-aminoisobutyric acid-containing peptides produced by Trichoderma species. Here, we studied the production of peptaibols by Trichoderma atroviride O1 and evaluated their antibacterial and anticancer activity against drug-sensitive [...] Read more.
Fighting resistance to antibiotics and chemotherapeutics has brought bioactive peptides to the fore. Peptaibols are short α-aminoisobutyric acid-containing peptides produced by Trichoderma species. Here, we studied the production of peptaibols by Trichoderma atroviride O1 and evaluated their antibacterial and anticancer activity against drug-sensitive and multidrug-resistant bacterium and cancer cell lines. This was substantiated by an analysis of the activity of the peptaibol synthetase-encoding gene. Atroviridins, 20-residue peptaibols were detected using MALDI-TOF mass spectrometry. Gram-positive bacteria were susceptible to peptaibol-containing extracts of T. atroviride O1. A synergic effect of extract constituents was possible, and the biolo-gical activity of extracts was pronounced in/after the peak of peptaibol synthetase activity. The growth of methicillin-resistant Staphylococcus aureus was reduced to just under 10% compared to the control. The effect of peptaibol-containing extracts was strongly modulated by the lipoteichoic acid and only slightly by the horse blood serum present in the cultivation medium. Peptaibol-containing extracts affected the proliferation of human breast cancer and human ovarian cancer cell lines in a 2D model, including the multidrug-resistant sublines. The peptaibols influenced the size and compactness of the cell lines in a 3D model. Our findings indicate the molecular basis of peptaibol production in T. atroviride O1 and the potential of its peptaibol-containing extracts as antimicrobial/anticancer agents. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Europe III)
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19 pages, 5140 KiB  
Article
Biological Effects on μ-Receptors Affinity and Selectivity of Arylpropenyl Chain Structural Modification on Diazatricyclodecane Derivatives
by Sandra Piras, Gabriele Murineddu, Giovanni Loriga, Antonio Carta, Enrica Battistello, Stefania Merighi, Stefania Gessi, Paola Corona, Battistina Asproni, Roberta Ibba, Veronika Temml, Daniela Schuster and Gérard Aimè Pinna
Molecules 2021, 26(18), 5448; https://doi.org/10.3390/molecules26185448 - 7 Sep 2021
Cited by 3 | Viewed by 1673
Abstract
Opioid analgesics are clinically used to relieve severe pain in acute postoperative and cancer pain, and also in the long term in chronic pain. The analgesic action is mediated by μ-, δ-, and κ-receptors, but currently, with few exceptions for k-agonists, μ-agonists are [...] Read more.
Opioid analgesics are clinically used to relieve severe pain in acute postoperative and cancer pain, and also in the long term in chronic pain. The analgesic action is mediated by μ-, δ-, and κ-receptors, but currently, with few exceptions for k-agonists, μ-agonists are the only ones used in therapy. Previously synthesized compounds with diazotricyclodecane cores (DTDs) have shown their effectiveness in binding opioid receptors. Fourteen novel diazatricyclodecanes belonging to the 9-propionyl-10-substituted-9,10-diazatricyclo[4.2.1.12,5]decane (compounds 2023, 53, 57 and 59) and 2-propionyl-7-substituted-2,7-diazatricyclo[4.4.0.03,8]decane (compounds 2427, 54, 58 and 60) series, respectively, have been synthesized and their ability to bind to the opioid μ-, δ- and κ-receptors was evaluated. Five of these derivatives, compounds 20, 21, 24, 26 and 53, showed μ-affinity in the nanomolar range with a negligible affinity towards δ- and κ-receptors and high μ-receptor selectivity. The synthesized compounds showed μ-receptor selectivity higher than those of previously reported methylarylcinnamyl analogs. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Europe III)
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15 pages, 2098 KiB  
Article
Theoretical Study of 2-(Trifluoromethyl)phenothiazine Derivatives with Two Hydroxyl Groups in the Side Chain-DFT and QTAIM Computations
by Andrzej Poła, Anna Palko-Łabuz and Kamila Środa-Pomianek
Molecules 2021, 26(17), 5242; https://doi.org/10.3390/molecules26175242 - 29 Aug 2021
Cited by 1 | Viewed by 1939
Abstract
Phenothiazines are known as synthetic antipsychotic drugs that exhibit a wide range of biological effects. Their properties result from the structure and variability of substituents in the heterocyclic system. It is known that different quantum chemical properties have a significant impact on drug [...] Read more.
Phenothiazines are known as synthetic antipsychotic drugs that exhibit a wide range of biological effects. Their properties result from the structure and variability of substituents in the heterocyclic system. It is known that different quantum chemical properties have a significant impact on drug behavior in the biological systems. Thus, due to the diversity in the chemical structure of phenothiazines as well as other drugs containing heterocyclic systems, quantum chemical calculations provide valuable methods in predicting their activity. In our study, DFT computations were applied to show some thermochemical parameters (bond dissociation enthalpy—BDE, ionization potential—IP, proton dissociation enthalpy—PDE, proton affinity—PA, and electrontransfer enthalpy—ETE) describing the process of releasing the hydrogen/proton from the hydroxyl group in the side chain of four 2-(trifluoromethyl)phenothiazine (TFMP) derivatives and fluphenazine (FLU). Additional theoretical analysis was carried out based on QTAIM theory. The results allowed theoretical determination of the ability of compounds to scavenge free radicals. In addition, the intramolecular hydrogen bond (H-bond) between the H-atom of the hydroxyl group and the N-atom located in the side chain of the investigated compounds has been identified and characterized. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Europe III)
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Review

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17 pages, 1331 KiB  
Review
New Generation of Meso and Antiprogestins (SPRMs) into the Osteoporosis Approach
by Magdalena Woźniczka and Katarzyna Błaszczak-Świątkiewicz
Molecules 2021, 26(21), 6491; https://doi.org/10.3390/molecules26216491 - 27 Oct 2021
Cited by 2 | Viewed by 2667
Abstract
Receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) play key roles in bone metabolism and the immune system. The RANK/RANKL complex has also been shown to be critical in the formation of mammary epithelia cells. The female hormones estradiol and [...] Read more.
Receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) play key roles in bone metabolism and the immune system. The RANK/RANKL complex has also been shown to be critical in the formation of mammary epithelia cells. The female hormones estradiol and progesterone closely control the action of RANKL with RANK. Blood concentration of these sex hormones in the postmenopausal period leads to an increase in RANK/RANKL signaling and are a major cause of women’s osteoporosis, characterized by altered bone mineralization. Knowledge of the biochemical relationships between hormones and RANK/RANKL signaling provides the opportunity to design novel therapeutic agents to inhibit bone loss, based on the anti-RANKL treatment and inhibition of its interaction with the RANK receptor. The new generation of both anti- and mesoprogestins that inhibit the NF-κB-cyclin D1 axis and blocks the binding of RANKL to RANK can be considered as a potential source of new RANK receptor ligands with anti-RANKL function, which may provide a new perspective into osteoporosis treatment itself as well as limit the osteoporosis rise during breast cancer metastasis to the bone. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Europe III)
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31 pages, 18964 KiB  
Review
Soft Contact Lenses as Drug Delivery Systems: A Review
by Iwona Rykowska, Iwona Nowak and Rafał Nowak
Molecules 2021, 26(18), 5577; https://doi.org/10.3390/molecules26185577 - 14 Sep 2021
Cited by 40 | Viewed by 8706
Abstract
This review describes the role of contact lenses as an innovative drug delivery system in treating eye diseases. Current ophthalmic drug delivery systems are inadequate, particularly eye drops, which allow about 95% of the active substance to be lost through tear drainage. According [...] Read more.
This review describes the role of contact lenses as an innovative drug delivery system in treating eye diseases. Current ophthalmic drug delivery systems are inadequate, particularly eye drops, which allow about 95% of the active substance to be lost through tear drainage. According to the literature, many interdisciplinary studies have been carried out on the ability of contact lenses to increase the penetration of topical therapeutic agents. Contact lenses limit drug loss by releasing the medicine into two layers of tears on either side of the contact lens, eventually extending the time of contact with the ocular surface. Thanks to weighted soft contact lenses, a continuous release of the drug over an extended period is possible. This article reviewed the various techniques to deliver medications through contact lenses, examining their advantages and disadvantages. In addition, the potential of drug delivery systems based on contact lenses has been extensively studied. Full article
(This article belongs to the Special Issue Medicinal Chemistry in Europe III)
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