Perspectives and Challenges in the Synthesis and Analysis of Drugs—49th Conference “Synthesis and Analysis of Drugs” (SAD 2021)

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 12290

Special Issue Editors

Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
Interests: antimicrobial; antimycobacterial; heterocyclic chemistry; structure-based drug design; computer-aided drug design
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Guest Editor
Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
Interests: antimicrobials; antimycobacterials; enzyme inhibitors; peptide carriers; prodrugs
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
1. Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 01328 Dresden, Germany
2. Faculty of Chemistry and Food Chemistry, Technische Universität Dresden, 01069 Dresden, Germany
Interests: development of radiotracers for molecular imaging; enzyme inhibitors; synthesis of radiolabelled compounds; radiopharmacology

Special Issue Information

Dear Colleagues,

The Special Issue collects selected papers from the 49th conference “Synthesis and Analysis of Drugs” (SAD 2021). The conference is jointly organized by the Faculty of Pharmacy in Hradec Králové, Charles University (the most prestigious university in the Czech Republic) and by the Czech Pharmaceutical Society. Registration for the virtual conference is still possible at least until 15 August at https://www.faf.cuni.cz/SAL2021/.

The 49th conference “Synthesis and Analysis of Drugs” (SAD 2021) will be held online on 16–17 September 2021. SAD meetings discuss current challenges in the field of medicinal chemistry, pharmaceutical analysis, and related disciplines. As it has been done in the previous forty-eight editions, particular emphasis has been set on opportunities for confirmed speakers and early career and youth scientists to present new results and stimulate interactions between academia and industry. The very high quality of the scientific presentations has incited the organizing committee to launch a Special Issue with the objective of discovering new researchers with high potential.

SAD 2021 participants are cordially invited to contribute original research papers or reviews to this Special Issue of Pharmaceuticals.

The following topics will be covered:

  • Bioorganic and Pharmaceutical (Medicinal) Chemistry
  • Pharmaceutical Analysis and Bioanalytical chemistry

Dr. Jan Zitko
Dr. Martin Krátký
Dr. Reik Löser
Guest Editors

Manuscript Submission Information

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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. Pharmaceuticals is an international peer-reviewed open access monthly 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 2900 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

  • bioanalytical chemistry
  • bioorganic chemistry
  • computer-aided drug design
  • medicinal chemistry
  • pharmaceutical analysis
  • pharmaceutical chemistry

Published Papers (5 papers)

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Research

18 pages, 2825 KiB  
Article
Application of Plackett–Burman Design for Spectrochemical Determination of the Last-Resort Antibiotic, Tigecycline, in Pure Form and in Pharmaceuticals: Investigation of Thermodynamics and Kinetics
by Ahmed S. El-Shafie, Aseel Yousef and Marwa El-Azazy
Pharmaceuticals 2022, 15(7), 888; https://doi.org/10.3390/ph15070888 - 19 Jul 2022
Cited by 6 | Viewed by 1648
Abstract
Tigecycline (TIGC) reacts with 7,7,8,8-tetracyanoquinodimethane (TCNQ) to form a bright green charge transfer complex (CTC). The spectrum of the CTC showed multiple charge transfer bands with a major peak at 843 nm. The Plackett–Burman design (PBD) was used to investigate the process variables [...] Read more.
Tigecycline (TIGC) reacts with 7,7,8,8-tetracyanoquinodimethane (TCNQ) to form a bright green charge transfer complex (CTC). The spectrum of the CTC showed multiple charge transfer bands with a major peak at 843 nm. The Plackett–Burman design (PBD) was used to investigate the process variables with the objective being set to obtaining the maximum absorbance and thus sensitivity. Four variables, three of which were numerical (temperature—Temp; reagent volume—RV; reaction time—RT) and one non-numerical (diluting solvent—DS), were studied. The maximum absorbance was achieved using a factorial blend of Temp: 25 °C, RV: 0.50 mL, RT: 60 min, and acetonitrile (ACN) as a DS. The molecular composition that was investigated using Job’s method showed a 1:1 CTC. The method’s validation was performed following the International Conference of Harmonization (ICH) guidelines. The linearity was achieved over a range of 0.5–10 µg mL−1 with the limits of detection (LOD) and quantification (LOQ) of 166 and 504 ng mL−1, respectively. The method was applicable to TIGC per se and in formulations without interferences from common additives. The application of the Benesi–Hildebrand equation revealed the formation of a stable complex with a standard Gibbs free energy change (∆) value of −26.42 to −27.95 kJ/mol. A study of the reaction kinetics revealed that the CTC formation could be best described using a pseudo-first-order reaction. Full article
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19 pages, 1819 KiB  
Article
Antistaphylococcal Activities and ADME-Related Properties of Chlorinated Arylcarbamoylnaphthalenylcarbamates
by Tomas Gonec, Dominika Pindjakova, Lucia Vrablova, Tomas Strharsky, Hana Michnova, Tereza Kauerova, Peter Kollar, Michal Oravec, Izabela Jendrzejewska, Alois Cizek and Josef Jampilek
Pharmaceuticals 2022, 15(6), 715; https://doi.org/10.3390/ph15060715 - 5 Jun 2022
Cited by 4 | Viewed by 1935
Abstract
Pattern 1-hydroxy-N-(2,4,5-trichlorophenyl)-2-naphthamide and the thirteen original carbamates derived from it were prepared and characterized. All the compounds were tested against Staphylococcus aureus ATCC 29213 as a reference and quality control strain and in addition against three clinical isolates of methicillin-resistant S. [...] Read more.
Pattern 1-hydroxy-N-(2,4,5-trichlorophenyl)-2-naphthamide and the thirteen original carbamates derived from it were prepared and characterized. All the compounds were tested against Staphylococcus aureus ATCC 29213 as a reference and quality control strain and in addition against three clinical isolates of methicillin-resistant S. aureus (MRSA). Moreover, the compounds were evaluated against Enterococcus faecalis ATCC 29212, and preliminary in vitro cytotoxicity of the compounds was assessed using the human monocytic leukemia cell line (THP-1). The lipophilicity of the prepared compounds was experimentally determined and correlated with biological activity. While pattern anilide had no antibacterial activity, the prepared carbamates demonstrated high antistaphylococcal activity comparable to the used standards (ampicillin and ciprofloxacin), which unfortunately were ineffective against E. feacalis. 2-[(2,4,5-Trichlorophenyl)carba- moyl]naphthalen-1-yl ethylcarbamate (2) and 2-[(2,4,5-trichlorophenyl)carbamoyl]naphthalen-1-yl butylcarbamate (4) expressed the nanomolar minimum inhibitory concentrations (MICs 0.018–0.064 μM) against S. aureus and at least two other MRSA isolates. Microbicidal effects based on the minimum bactericidal concentrations (MBCs) against all the tested staphylococci were found for nine carbamates, while 2-[(2,4,5-trichlorophenyl)carbamoyl]naphthalen-1-yl heptylcarbamate (7) and 2-[(2,4,5-trichlorophenyl)carbamoyl]naphthalen-1-yl (4-phenylbutyl)carbamate (14) demonstrated MBCs in the range of 0.124–0.461 μM. The selectivity index (SI) for most investigated carbamates was >20 and for some derivatives even >100. The performed tests did not show an effect on the damage to the bacterial membrane, while the compounds were able to inhibit the respiratory chain of S. aureus. Full article
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13 pages, 2211 KiB  
Article
Magnesium Phthalocyanines and Tetrapyrazinoporphyrazines: The Influence of a Solvent and a Delivery System on a Dissociation of Central Metal in Acidic Media
by Michaela Kolarova, Anita Mulaku, Miroslav Miletin, Veronika Novakova and Petr Zimcik
Pharmaceuticals 2022, 15(4), 409; https://doi.org/10.3390/ph15040409 - 27 Mar 2022
Cited by 1 | Viewed by 2123
Abstract
Magnesium complexes of phthalocyanines (Pcs) and their aza-analogues have a great potential in medical applications or fluorescence detection. They are known to demetallate to metal-free ligands in acidic environments, however, detailed investigation of this process and its possible prevention is lacking. In this [...] Read more.
Magnesium complexes of phthalocyanines (Pcs) and their aza-analogues have a great potential in medical applications or fluorescence detection. They are known to demetallate to metal-free ligands in acidic environments, however, detailed investigation of this process and its possible prevention is lacking. In this work, a conversion of lipophilic and water-soluble magnesium complexes of Pcs and tetrapyrazinoporphyrazines (TPyzPzs) to metal-free ligands was studied in relation to the acidity of the environment (organic solvent, water) including the investigation of the role of delivery systems (microemulsion or liposomes) in improvement in their acido-stability. The mechanism of the demetallation in organic solvents was based on an acidoprotolytic mechanism with the protonation of the azomethine nitrogen as the first step and a subsequent conversion to non-protonated metal-free ligands. In water, the mechanism seemed to be solvoprotolytic without any protonated intermediate. The water-soluble magnesium complexes were stable in a buffer with a physiological pH 7.4 while a time-dependent demetallation was observed in acidic pH. The demetallation was immediate at pH < 2 while the full conversion to metal-free ligand was done within 10 min and 45 min for TPyzPzs at pH 3 and pH 4, respectively. Incorporation of lipophilic magnesium complexes into microemulsion or liposomes substantially decreased the rate of the demetallation with the latter delivery system being much more efficient in the protection from the acidic environment. A comparison of two different macrocyclic cores revealed significantly higher kinetic inertness of magnesium TPyzPz complexes than their Pc analogues. Full article
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14 pages, 8462 KiB  
Article
Determination of Phloridzin and Other Phenolic Compounds in Apple Tree Leaves, Bark, and Buds Using Liquid Chromatography with Multilayered Column Technology and Evaluation of the Total Antioxidant Activity
by Anežka Adamcová, Aleš Horna and Dalibor Šatínský
Pharmaceuticals 2022, 15(2), 244; https://doi.org/10.3390/ph15020244 - 18 Feb 2022
Cited by 9 | Viewed by 2260
Abstract
Apples are known to be a rich source of phenolic compounds, however detailed studies about their content in the individual parts of apple trees are reported rarely. For this purpose, we tested various stationary phases for the determination of phenolic compounds in leaves, [...] Read more.
Apples are known to be a rich source of phenolic compounds, however detailed studies about their content in the individual parts of apple trees are reported rarely. For this purpose, we tested various stationary phases for the determination of phenolic compounds in leaves, bark, and buds. Phloridzin, phloretin, chlorogenic acid, rutin, and quercitrin were analyzed with high performance liquid chromatography coupled with diode array detection. A YMC Triart C18-ExRS 150 × 4.6 mm, 5 µm particle size analytical column with multilayered particle technology was used. The separation was performed with a mobile phase that consisted of acetonitrile and 0.1% phosphoric acid, according to the gradient program, at a flow rate of 1 mL/min for 12.50 min. The concentration of phenolic compounds from 13 cultivars was in the range of 64.89–106.01 mg/g of dry weight (DW) in leaves, 70.81–113.18 mg/g DW in bark, and 100.68–139.61 mg/g DW in buds. Phloridzin was a major compound. The total antioxidant activity was measured using flow analysis and the correlation with the total amount of phenolic compounds was found. This finding can lead to the re-use of apple tree material to isolate substances that can be utilized in the food, pharmaceutical, or cosmetics industries. Full article
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30 pages, 4989 KiB  
Article
Novel Aminoguanidine Hydrazone Analogues: From Potential Antimicrobial Agents to Potent Cholinesterase Inhibitors
by Martin Krátký, Šárka Štěpánková, Klára Konečná, Katarína Svrčková, Jana Maixnerová, Markéta Švarcová, Ondřej Janďourek, František Trejtnar and Jarmila Vinšová
Pharmaceuticals 2021, 14(12), 1229; https://doi.org/10.3390/ph14121229 - 26 Nov 2021
Cited by 10 | Viewed by 3074
Abstract
A series of thirty-one hydrazones of aminoguanidine, nitroaminoguanidine, 1,3-diaminoguanidine, and (thio)semicarbazide were prepared from various aldehydes, mainly chlorobenzaldehydes, halogenated salicylaldehydes, 5-nitrofurfural, and isatin (yields of 50–99%). They were characterized by spectral methods. Primarily, they were designed and evaluated as potential broad-spectrum antimicrobial agents. [...] Read more.
A series of thirty-one hydrazones of aminoguanidine, nitroaminoguanidine, 1,3-diaminoguanidine, and (thio)semicarbazide were prepared from various aldehydes, mainly chlorobenzaldehydes, halogenated salicylaldehydes, 5-nitrofurfural, and isatin (yields of 50–99%). They were characterized by spectral methods. Primarily, they were designed and evaluated as potential broad-spectrum antimicrobial agents. The compounds were effective against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus with minimum inhibitory concentrations (MIC) from 7.8 µM, as well as Gram-negative strains with higher MIC. Antifungal evaluation against yeasts and Trichophyton mentagrophytes found MIC from 62.5 µM. We also evaluated inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The compounds inhibited both enzymes with IC50 values of 17.95–54.93 µM for AChE and ≥1.69 µM for BuChE. Based on the substitution, it is possible to modify selectivity for a particular cholinesterase as we obtained selective inhibitors of either AChE or BuChE, as well as balanced inhibitors. The compounds act via mixed-type inhibition. Their interactions with enzymes were studied by molecular docking. Cytotoxicity was assessed in HepG2 cells. The hydrazones differ in their toxicity (IC50 from 5.27 to >500 µM). Some of the derivatives represent promising hits for further development. Based on the substitution pattern, it is possible to modulate bioactivity to the desired one. Full article
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