Applied Sciences

Editorial

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2 pages, 164 KiB

Open AccessEditorial

Special Issue: Advances in the Synthesis of Biologically Important Intermediates/Drugs

by Tricia Naicker

Appl. Sci. 2023, 13(4), 2390; https://doi.org/10.3390/app13042390 - 13 Feb 2023

Viewed by 880

Abstract

Chemical synthesis is a cornerstone of the development of medicinal chemistry, forming the basis for discovering compounds with new physical and/or biological properties [...] Full article

(This article belongs to the Special Issue Advances in the Synthesis of Biologically Important Intermediates/Drugs)

Research

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15 pages, 2954 KiB

Open AccessArticle

Synthesis and Physicochemical Properties of Cefepime Derivatives Suitable for Labeling with Gallium-68

by Przemysław Koźmiński, Kinga Żelechowska-Matysiak and Ewa Gniazdowska

Appl. Sci. 2023, 13(8), 5019; https://doi.org/10.3390/app13085019 - 17 Apr 2023

Viewed by 1176

Abstract

Bone and soft tissue infections are potentially life-threatening and require immediate and intensive treatment. However, there is still no single diagnostic method that can reliably confirm or rule out such conditions. Imaging with radiopharmaceuticals (i.e., scintigraphy) is a powerful diagnostic tool in the [...] Read more.

Bone and soft tissue infections are potentially life-threatening and require immediate and intensive treatment. However, there is still no single diagnostic method that can reliably confirm or rule out such conditions. Imaging with radiopharmaceuticals (i.e., scintigraphy) is a powerful diagnostic tool in the management of patients with infectious or inflammatory diseases. In this work, a new and efficient way to modify the thiazole ring of the cefepime molecule has been proposed and experimentally verified. The developed organic synthesis routes allow for the coupling of the appropriate complexing ligand of the gallium-68 radionuclide with cefepime. The new NODAGA-Glu-CFM conjugate was radiolabeled with gallium-68 with a high yield and showed full stability in human serum. In addition, the [⁶⁸Ga]Ga-NODAGA-Glu-CFM radioconjugate was hydrophilic and positively charged. Therefore, on the basis of these results, the [⁶⁸Ga]Ga-NODAGA-Glu-CFM radioconjugate might be considered as a new promising radioconjugate for the diagnosis of bacterial infections. Full article

(This article belongs to the Special Issue Advances in the Synthesis of Biologically Important Intermediates/Drugs)

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13 pages, 3191 KiB

Open AccessArticle

Modification of 6,7-Dichloro-5,8-Quinolinedione at C2 Position: Synthesis, Quantum Chemical Properties, and Activity against DT-Diaphorase Enzyme

by Monika Kadela-Tomanek, Ewa Bębenek and Elwira Chrobak

Appl. Sci. 2023, 13(3), 1530; https://doi.org/10.3390/app13031530 - 24 Jan 2023

Cited by 1 | Viewed by 1081

Abstract

This research presents a synthesis and characterization of new 6,7-dichloro-5,8-quinolinedione derivatives with various groups at the C2 position. Chemical structures were examined by the spectroscopic methods. The quantum chemical parameters calculated using the DFT method showed that these derivatives are highly reactive towards [...] Read more.

This research presents a synthesis and characterization of new 6,7-dichloro-5,8-quinolinedione derivatives with various groups at the C2 position. Chemical structures were examined by the spectroscopic methods. The quantum chemical parameters calculated using the DFT method showed that these derivatives are highly reactive towards the nucleophilic target. The molecular electrostatic potential map (MEP) showed that nucleophilic regions are localized near the nitrogen atom and the formyl group. Introduction of the hydroxyl or formyl groups at the C2 position led to the formation of an additional nucleophilic region. New compounds were tested as substrates for the NQO1 protein. An enzymatic study showed that derivatives are a good substrate for the NQO1 enzyme. Moreover, it was shown that the enzymatic conversion rates depend on the type of substituent at the C2 position of the 5,8-quinolinedione scaffold. A molecular docking study was used to study the interaction between new derivatives and the NQO1 protein. The arrangement and type of interactions between derivatives and the NQO1 enzyme depended on the type of substituent at the C2 position. A derivative with the hydroxyl group at this position was found to form an additional hydrogen bond between the formyl group and the tyrosine. Full article

(This article belongs to the Special Issue Advances in the Synthesis of Biologically Important Intermediates/Drugs)

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14 pages, 3744 KiB

Open AccessArticle

Probing New Antileukemia Agents That Target FLT3 and BCL-2 from Traditional Concoctions through a Combination of Mass Spectrometry Analysis and Consensus Docking Methods

by Adebayo A. Adeniyi, Joy Nkechinyere Adeniyi, Manimbulu Nlooto and Parvesh Singh

Appl. Sci. 2022, 12(22), 11611; https://doi.org/10.3390/app122211611 - 15 Nov 2022

Cited by 1 | Viewed by 1170

Abstract

The search for new chemotherapeutics against leukemia is of great interest to researchers, owing to the limitation of the current drugs. In this research, new drug candidates against leukemia were probed through liquid chromatography-mass spectrometer (LC-MS) analysis of three traditional herbal concoctions, that [...] Read more.

The search for new chemotherapeutics against leukemia is of great interest to researchers, owing to the limitation of the current drugs. In this research, new drug candidates against leukemia were probed through liquid chromatography-mass spectrometer (LC-MS) analysis of three traditional herbal concoctions, that provide the phytochemical profile of the samples. The identified compounds from the LC-MS were modeled for the analysis of their antileukemia activities, by using five different consensus methods, to combine the seven docking scores. The consensus methods are used to combine the docking scores to avoid losing promising drug candidates, due to a poor reproducibility of the docking scores across the different packages, due to differences in the scoring functions and training sets across the docking packages. The libraries of the potential drug candidates from the concoctions were constructed by searching the NIST database for molecules with a similar MS fragmentation. Venetoclax and gilteritinib, that target FLT3 and BCL-2 were ranked among the top hits, indicating the efficiency of this protocol without missing any potential drug. The results ranked rescinnamine and bisacodyl as new potential antileukemia agents that targets FLAT3, and BCL-2, including the mutated BCL-2 G101V receptor, that is known to be resistant to treatment with venetoclax. Full article

(This article belongs to the Special Issue Advances in the Synthesis of Biologically Important Intermediates/Drugs)

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15 pages, 5908 KiB

Open AccessArticle

Anthraquinone Rhein Exhibits Antibacterial Activity against Staphylococcus aureus

by Federica Dell’Annunziata, Veronica Folliero, Francesca Palma, Valeria Crudele, Emiliana Finamore, Giuseppina Sanna, Aldo Manzin, Anna De Filippis, Massimiliano Galdiero and Gianluigi Franci

Appl. Sci. 2022, 12(17), 8691; https://doi.org/10.3390/app12178691 - 30 Aug 2022

Cited by 8 | Viewed by 1937

Abstract

Staphylococcus aureus (S. aureus) represents an important pathogen of clinical relevance, causing a wide variety of symptoms. The broad distribution of multidrug-resistant strains necessarily demands new antibacterial agents for the treatment of S. aureus infections. The aim of this study was [...] Read more.

Staphylococcus aureus (S. aureus) represents an important pathogen of clinical relevance, causing a wide variety of symptoms. The broad distribution of multidrug-resistant strains necessarily demands new antibacterial agents for the treatment of S. aureus infections. The aim of this study was to assess the antibacterial activity of plant-derived compounds, pure 4,5″-dihydroxy-anthraquinone-2-carboxylic acid (Rhein), against standard and clinical isolated S. aureus strains. The hemolysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were used to determine the cytotoxicity on human erythrocytes and bronchial epithelial cells after treatment with Rhein. The antibacterial effect was assessed via disk diffusion test, broth microdilution methods, time-killing assays and live–dead evaluation (50–0.39 µg/mL). Rhein effect on the hemolytic activity of α-toxin and catalase were estimated. Moreover, crystal violet (CV) assay evaluated its impact on biofilm biomass. The compound exhibited 50% cytotoxic concentration (CC₅₀) and 50% hemolysis concentration (EC₅₀) of 43.6 and >50 µg/mL, respectively. The minimum inhibitory concentration (MIC) of Rhein was 12.5 µg/mL for all tested strains, exerting bacteriostatic action. MIC and sub-MIC concentrations of Rhein significantly reduced hemolytic and catalase activities, impairing the major virulence factors of S. aureus strains. Rhein also reduced biofilm biomass in a dose-dependent manner, reaching rates of about 50% eradication at a dose of 50 µg/mL. These findings suggest that Rhein could represent a promising therapeutic option for the treatment of S. aureus infections. Full article

(This article belongs to the Special Issue Advances in the Synthesis of Biologically Important Intermediates/Drugs)

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11 pages, 4948 KiB

Open AccessArticle

Antiproliferative Activity of Aminobenzylnaphthols Deriving from the Betti Reaction

by Rosanna Mallamaci, Maria Annunziata M. Capozzi and Cosimo Cardellicchio

Appl. Sci. 2022, 12(15), 7779; https://doi.org/10.3390/app12157779 - 2 Aug 2022

Cited by 6 | Viewed by 1619

Abstract

Two aminobenzylnaphthols, which are representative items of the family of compounds synthesized with the Betti reaction, were investigated as antiproliferative agents against adenocarcinoma human colorectal (Caco-2) and human neuroblastoma (SH-SY5Y) cell lines, using cisplatin as a positive control. A better antiproliferative activity was [...] Read more.

Two aminobenzylnaphthols, which are representative items of the family of compounds synthesized with the Betti reaction, were investigated as antiproliferative agents against adenocarcinoma human colorectal (Caco-2) and human neuroblastoma (SH-SY5Y) cell lines, using cisplatin as a positive control. A better antiproliferative activity was recorded after 24 h of incubation for the first tested molecule, whereas the other one was more effective after 72 h of incubation. These results support the hypothesis that both of the tested aminobenzylnaphthols could potentially be endowed with a biological activity. Full article

(This article belongs to the Special Issue Advances in the Synthesis of Biologically Important Intermediates/Drugs)

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Review

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22 pages, 7518 KiB

Open AccessReview

A Look at the Importance of Chirality in Drug Activity: Some Significative Examples

by Jessica Ceramella, Domenico Iacopetta, Angelica Franchini, Michele De Luca, Carmela Saturnino, Inmaculada Andreu, Maria Stefania Sinicropi and Alessia Catalano

Appl. Sci. 2022, 12(21), 10909; https://doi.org/10.3390/app122110909 - 27 Oct 2022

Cited by 27 | Viewed by 11422

Abstract

Chirality plays an important role in the development of many pharmaceuticals, being a general property of ‘handedness’; nevertheless, a large number of pharmaceuticals are still marketed and administered as racemates. Chirality is all around and even within us; indeed, receptors and enzymes are [...] Read more.

Chirality plays an important role in the development of many pharmaceuticals, being a general property of ‘handedness’; nevertheless, a large number of pharmaceuticals are still marketed and administered as racemates. Chirality is all around and even within us; indeed, receptors and enzymes are chiral entities and interact in a specific manner with chiral drugs. Consequently, controlling enantiomeric purity and isolating the enantiomers from chiral drugs remains a crucial subject for analytical, clinical, and regulatory purposes, thus, improving the drug safety profile. The classical examples of spontaneous enantiomerization and severe toxicity related to chirality are represented by ibuprofen and thalidomide, respectively, but numerous other cases have been reported in the literature. This review intends to offer a brief overview on the most common chiral drugs used in therapy for the treatment of various diseases. Full article

(This article belongs to the Special Issue Advances in the Synthesis of Biologically Important Intermediates/Drugs)

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17 pages, 8799 KiB

Open AccessReview

Arylation Reactions in the Synthesis of Biologically Important 2,5-Diaryl-1,3,4-Oxadiazoles

by Monika Olesiejuk and Agnieszka Kudelko

Appl. Sci. 2022, 12(15), 7806; https://doi.org/10.3390/app12157806 - 3 Aug 2022

Cited by 4 | Viewed by 1616

Abstract

Apart from carbon atoms, some cyclic molecules contain other elements and play an extraordinary role in human life. Among these systems, 1,3,4-oxadiazole derivatives deserve special attention due to their biological properties such as antibacterial, antifungal, antitumor, and anti-inflammatory properties. They are commonly used [...] Read more.

Apart from carbon atoms, some cyclic molecules contain other elements and play an extraordinary role in human life. Among these systems, 1,3,4-oxadiazole derivatives deserve special attention due to their biological properties such as antibacterial, antifungal, antitumor, and anti-inflammatory properties. They are commonly used in pharmacology, as well as in fungicidal, herbicidal, and insecticidal agricultural applications. The 1,3,4-oxadiazole fragment is connected directly to other aromatic systems and can be found in the structure of some commercially available drugs, or in potential drug candidates in the final pharmacological testing phase. Therefore, scientists are looking for new hybrid materials based on 1,3,4-oxadiazoles and other biologically active molecules. The most popular methods for constructing new carbon–carbon bonds between two aromatic species include direct arylation, condensation, and cross-coupling reactions. This review article, comprising the literature from 2009 to 2022, discusses a number of arylation reactions in the synthesis of 2,5-diaryl-1,3,4-oxadiazole derivatives. Full article

(This article belongs to the Special Issue Advances in the Synthesis of Biologically Important Intermediates/Drugs)

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