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14 pages, 1066 KiB

Open AccessArticle

Synthesis and Evaluation of Chalcone-Quinoline Based Molecular Hybrids as Potential Anti-Malarial Agents

by Bonani Vinindwa, Godwin Akpeko Dziwornu and Wayiza Masamba

Molecules 2021, 26(13), 4093; https://doi.org/10.3390/molecules26134093 - 05 Jul 2021

Cited by 14 | Viewed by 2839

Abstract

Molecular hybridization is a drug discovery strategy that involves the rational design of new chemical entities by the fusion (usually via a covalent linker) of two or more drugs, both active compounds and/or pharmacophoric units recognized and derived from known bioactive molecules. The [...] Read more.

Molecular hybridization is a drug discovery strategy that involves the rational design of new chemical entities by the fusion (usually via a covalent linker) of two or more drugs, both active compounds and/or pharmacophoric units recognized and derived from known bioactive molecules. The expected outcome of this chemical modification is to produce a new hybrid compound with improved affinity and efficacy compared to the parent drugs. Additionally, this strategy can result in compounds presenting modified selectivity profiles, different and/or dual modes of action, reduced undesired side effects and ultimately lead to new therapies. In this study, molecular hybridization was used to generate new molecular hybrids which were tested against the chloroquine sensitive (NF54) strain of P. falciparum. To prepare the new molecular hybrids, the quinoline nucleus, one of the privileged scaffolds, was coupled with various chalcone derivatives via an appropriate linker to produce a total of twenty-two molecular hybrids in 11%–96% yield. The synthesized compounds displayed good antiplasmodial activity with IC₅₀ values ranging at 0.10–4.45 μM. Full article

(This article belongs to the Special Issue Quinolones: Chemistry and Biological Activities)

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24 pages, 14421 KiB

Open AccessArticle

Development and Validation of Stability-Indicating HPLC Methods for the Estimation of Lomefloxacin and Balofloxacin Oxidation Process under ACVA, H₂O₂, or KMnO₄ Treatment. Kinetic Evaluation and Identification of Degradation Products by Mass Spectrometry

by Barbara Żuromska-Witek, Paweł Żmudzki, Marek Szlósarczyk, Anna Maślanka and Urszula Hubicka

Molecules 2020, 25(22), 5251; https://doi.org/10.3390/molecules25225251 - 11 Nov 2020

Cited by 6 | Viewed by 2323

Abstract

The oxidation of lomefloxacin (LOM) and balofloxacin (BAL) under the influence of azo initiator of radical reactions of 4,4′-azobis(4-cyanopentanoic acid) (ACVA) and H₂O₂ was examined. Oxidation using H₂O₂ was performed at room temperature while using ACVA at [...] Read more.

The oxidation of lomefloxacin (LOM) and balofloxacin (BAL) under the influence of azo initiator of radical reactions of 4,4′-azobis(4-cyanopentanoic acid) (ACVA) and H₂O₂ was examined. Oxidation using H₂O₂ was performed at room temperature while using ACVA at temperatures: 40, 50, 60 °C. Additionally, the oxidation process of BAL under the influence of KMnO₄ in an acidic medium was investigated. New stability-indicating HPLC methods were developed in order to evaluate the oxidation process. Chromatographic analysis was carried out using the Kinetex 5u XB—C18 100A column, Phenomenex (Torrance, CA, USA) (250 × 4.6 mm, 5 μm particle size, core shell type). The chromatographic separation was achieved while using isocratic elution and a mobile phase with the composition of 0.05 M phosphate buffer (pH = 3.20 adjusted with o-phosphoric acid) and acetonitrile (87:13 v/v for LOM; 80:20 v/v for BAL). The column was maintained at 30 °C. The methods were validated according to the ICH guidelines, and it was found that they met the acceptance criteria. An oxidation process followed kinetics of the second order reaction. The most probable structures of LOM and BAL degradation products formed were assigned by the UHPLC/MS/MS method. Full article

(This article belongs to the Special Issue Quinolones: Chemistry and Biological Activities)

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14 pages, 274 KiB

Open AccessArticle

Quinolone and Organophosphorus Insecticide Residues in Bivalves and Their Associated Risks in Taiwan

by Ching-Feng Wu, Ching-Hung Chen, Ching-Yang Wu, Chen-Si Lin, Yao-Chi Su, Ching-Fen Wu, Hsiao-Pei Tsai, Pei-Shan Fan, Chang-Hui Yeh, Wei-Cheng Yang and Geng-Ruei Chang

Molecules 2020, 25(16), 3636; https://doi.org/10.3390/molecules25163636 - 10 Aug 2020

Cited by 9 | Viewed by 2693

Abstract

Bivalves, such as freshwater clams (Corbicula fluminea) and hard clams (Meretrix lusoria), are the most extensive and widely grown shellfish in land-based ponds in Taiwan. However, few studies have examined the contamination of bivalves by quinolone and organophosphorus insecticides. [...] Read more.

Bivalves, such as freshwater clams (Corbicula fluminea) and hard clams (Meretrix lusoria), are the most extensive and widely grown shellfish in land-based ponds in Taiwan. However, few studies have examined the contamination of bivalves by quinolone and organophosphorus insecticides. Thus, we adapted an established procedure to analyze 8 quinolones and 12 organophosphorus insecticides using liquid and gas chromatography–tandem mass spectrometry. Surveys in Taiwan have not noted high residual levels of these chemicals in bivalve tissues. A total of 58 samples of freshwater or hard clams were obtained from Taiwanese aquafarms. We identified 0.03 mg/kg of enrofloxacin in one freshwater clam, 0.024 mg/kg of flumequine in one freshwater clam, 0.02 mg/kg of flumequine in one hard clam, 0.05 mg/kg of chlorpyrifos in one freshwater clam, 0.03 mg/kg of chlorpyrifos in one hard clam, and 0.02 mg/kg of trichlorfon in one hard clam. The results indicated that 5.17% of the samples had quinolone insecticide residues and 5.17% had organophosphorus residues. However, the estimated daily intake (EDI)/acceptable daily intake quotient (ADI) indicated no significant risk and no immediate health risk from the consumption of bivalves. These results provide a reference for the food-safety screening of veterinary drugs and pesticides in aquatic animals. Aquatic products should be frequently screened for residues of prohibited chemicals to safeguard human health. Full article

(This article belongs to the Special Issue Quinolones: Chemistry and Biological Activities)

Review

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42 pages, 5287 KiB

Open AccessReview

Biological Effects of Quinolones: A Family of Broad-Spectrum Antimicrobial Agents

by Ana R. Millanao, Aracely Y. Mora, Nicolás A. Villagra, Sergio A. Bucarey and Alejandro A. Hidalgo

Molecules 2021, 26(23), 7153; https://doi.org/10.3390/molecules26237153 - 25 Nov 2021

Cited by 53 | Viewed by 10287

Abstract

Broad antibacterial spectrum, high oral bioavailability and excellent tissue penetration combined with safety and few, yet rare, unwanted effects, have made the quinolones class of antimicrobials one of the most used in inpatients and outpatients. Initially discovered during the search for improved chloroquine-derivative [...] Read more.

Broad antibacterial spectrum, high oral bioavailability and excellent tissue penetration combined with safety and few, yet rare, unwanted effects, have made the quinolones class of antimicrobials one of the most used in inpatients and outpatients. Initially discovered during the search for improved chloroquine-derivative molecules with increased anti-malarial activity, today the quinolones, intended as antimicrobials, comprehend four generations that progressively have been extending antimicrobial spectrum and clinical use. The quinolone class of antimicrobials exerts its antimicrobial actions through inhibiting DNA gyrase and Topoisomerase IV that in turn inhibits synthesis of DNA and RNA. Good distribution through different tissues and organs to treat Gram-positive and Gram-negative bacteria have made quinolones a good choice to treat disease in both humans and animals. The extensive use of quinolones, in both human health and in the veterinary field, has induced a rise of resistance and menace with leaving the quinolones family ineffective to treat infections. This review revises the evolution of quinolones structures, biological activity, and the clinical importance of this evolving family. Next, updated information regarding the mechanism of antimicrobial activity is revised. The veterinary use of quinolones in animal productions is also considered for its environmental role in spreading resistance. Finally, considerations for the use of quinolones in human and veterinary medicine are discussed. Full article

(This article belongs to the Special Issue Quinolones: Chemistry and Biological Activities)

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26 pages, 11987 KiB

Open AccessReview

Bacterial Alkyl-4-quinolones: Discovery, Structural Diversity and Biological Properties

by Muhammad Saalim, Jessica Villegas-Moreno and Benjamin R. Clark

Molecules 2020, 25(23), 5689; https://doi.org/10.3390/molecules25235689 - 02 Dec 2020

Cited by 27 | Viewed by 4308

Abstract

The alkyl-4-quinolones (AQs) are a class of metabolites produced primarily by members of the Pseudomonas and Burkholderia genera, consisting of a 4-quinolone core substituted by a range of pendant groups, most commonly at the C-2 position. The history of this class of compounds [...] Read more.

The alkyl-4-quinolones (AQs) are a class of metabolites produced primarily by members of the Pseudomonas and Burkholderia genera, consisting of a 4-quinolone core substituted by a range of pendant groups, most commonly at the C-2 position. The history of this class of compounds dates back to the 1940s, when a range of alkylquinolones with notable antibiotic properties were first isolated from Pseudomonas aeruginosa. More recently, it was discovered that an alkylquinolone derivative, the Pseudomonas Quinolone Signal (PQS) plays a key role in bacterial communication and quorum sensing in Pseudomonas aeruginosa. Many of the best-studied examples contain simple hydrocarbon side-chains, but more recent studies have revealed a wide range of structurally diverse examples from multiple bacterial genera, including those with aromatic, isoprenoid, or sulfur-containing side-chains. In addition to their well-known antimicrobial properties, alkylquinolones have been reported with antimalarial, antifungal, antialgal, and antioxidant properties. Here we review the structural diversity and biological activity of these intriguing metabolites. Full article

(This article belongs to the Special Issue Quinolones: Chemistry and Biological Activities)

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27 pages, 2436 KiB

Open AccessReview

Quinolones: Mechanism, Lethality and Their Contributions to Antibiotic Resistance

by Natassja G. Bush, Isabel Diez-Santos, Lauren R. Abbott and Anthony Maxwell

Molecules 2020, 25(23), 5662; https://doi.org/10.3390/molecules25235662 - 01 Dec 2020

Cited by 141 | Viewed by 24530

Abstract

Fluoroquinolones (FQs) are arguably among the most successful antibiotics of recent times. They have enjoyed over 30 years of clinical usage and become essential tools in the armoury of clinical treatments. FQs target the bacterial enzymes DNA gyrase and DNA topoisomerase IV, where [...] Read more.

Fluoroquinolones (FQs) are arguably among the most successful antibiotics of recent times. They have enjoyed over 30 years of clinical usage and become essential tools in the armoury of clinical treatments. FQs target the bacterial enzymes DNA gyrase and DNA topoisomerase IV, where they stabilise a covalent enzyme-DNA complex in which the DNA is cleaved in both strands. This leads to cell death and turns out to be a very effective way of killing bacteria. However, resistance to FQs is increasingly problematic, and alternative compounds are urgently needed. Here, we review the mechanisms of action of FQs and discuss the potential pathways leading to cell death. We also discuss quinolone resistance and how quinolone treatment can lead to resistance to non-quinolone antibiotics. Full article

(This article belongs to the Special Issue Quinolones: Chemistry and Biological Activities)

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41 pages, 10397 KiB

Open AccessReview

Recent Advances in One-Pot Modular Synthesis of 2-Quinolones

by Wan Pyo Hong, Inji Shin and Hee Nam Lim

Molecules 2020, 25(22), 5450; https://doi.org/10.3390/molecules25225450 - 20 Nov 2020

Cited by 14 | Viewed by 4235

Abstract

It is known that 2-quinolones are broadly applicable chemical structures in medicinal and agrochemical research as well as various functional materials. A number of current publications about their synthesis and their applications emphasize the importance of these small molecules. The early synthetic chemistry [...] Read more.

It is known that 2-quinolones are broadly applicable chemical structures in medicinal and agrochemical research as well as various functional materials. A number of current publications about their synthesis and their applications emphasize the importance of these small molecules. The early synthetic chemistry originated from the same principle of the classical Friedländer and Knorr procedures for the preparation of quinolines. The analogous processes were developed by applying new synthetic tools such as novel catalysts, the microwave irradiation method, etc., whereas recent innovations in new bond forming reactions have allowed for novel strategies to construct the core structures of 2-quinolones beyond the bond disconnections based on two classical reactions. Over the last few decades, some reviews on structure-based, catalyst-based, and bioactivity-based studies have been released. In this focused review, we extensively surveyed recent examples of one-pot reactions, particularly in view of modular approaches. Thus, the contents are categorized as three major sections (two-, three-, and four-component reactions) according to the number of reagents that ultimately compose atoms of the core structures of 2-quinolones. The collected synthetic methods are discussed from the perspectives of strategy, efficiency, selectivity, and reaction mechanism. Full article

(This article belongs to the Special Issue Quinolones: Chemistry and Biological Activities)

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16 pages, 330 KiB

Open AccessReview

Optimization Strategies Aimed to Increase the Efficacy of Helicobacter pylori Eradication Therapies with Quinolones

by Javier P. Gisbert

Molecules 2020, 25(21), 5084; https://doi.org/10.3390/molecules25215084 - 02 Nov 2020

Cited by 11 | Viewed by 3069

Abstract

H. pylori infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. Fluoroquinolones such as levofloxacin, or more recently moxifloxacin or sitafloxacin, are efficacious alternatives to standard antibiotics for H. pylori eradication. The aim of the present review is to [...] Read more.

H. pylori infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. Fluoroquinolones such as levofloxacin, or more recently moxifloxacin or sitafloxacin, are efficacious alternatives to standard antibiotics for H. pylori eradication. The aim of the present review is to summarize the role of quinolone-based eradication therapies, mainly focusing on the optimization strategies aimed to increase their efficacy. Several meta-analyses have shown that, after failure of a first-line eradication treatment, a levofloxacin-containing rescue regimen is at least equally effective, and better tolerated, than the generally recommended bismuth quadruple regimen. Compliance with the levofloxacin regimens is excellent, and the safety profile is favourable. Higher cure rates have been reported with longer treatments (>10–14 days), and 500 mg levofloxacin daily is the recommended dose. Adding bismuth to the standard triple regimen (PPI-amoxicillin-levofloxacin) has been associated with encouraging results. Unfortunately, resistance to quinolones is easily acquired and is increasing in most countries, being associated with a decrease in the eradication rate of H. pylori. In summary, a quinolone (mainly levofloxacin)-containing regimen is an encouraging second-line (or even third-line) strategy, and a safe and simple alternative to bismuth quadruple therapy in patients whose previous H. pylori eradication therapy has failed. Full article

(This article belongs to the Special Issue Quinolones: Chemistry and Biological Activities)

35 pages, 5317 KiB

Open AccessReview

Quinolone Complexes with Lanthanide Ions: An Insight into their Analytical Applications and Biological Activity

by Ana-Mădălina Măciucă, Alexandra-Cristina Munteanu and Valentina Uivarosi

Molecules 2020, 25(6), 1347; https://doi.org/10.3390/molecules25061347 - 16 Mar 2020

Cited by 24 | Viewed by 5448

Abstract

Quinolones comprise a series of synthetic bactericidal agents with a broad spectrum of activity and good bioavailability. An important feature of these molecules is their capacity to bind metal ions in complexes with relevant biological and analytical applications. Interestingly, lanthanide ions possess extremely [...] Read more.

Quinolones comprise a series of synthetic bactericidal agents with a broad spectrum of activity and good bioavailability. An important feature of these molecules is their capacity to bind metal ions in complexes with relevant biological and analytical applications. Interestingly, lanthanide ions possess extremely attractive properties that result from the behavior of the internal 4f electrons, behavior which is not lost upon ionization, nor after coordination. Subsequently, a more detailed discussion about metal complexes of quinolones with lanthanide ions in terms of chemical and biological properties is made. These complexes present a series of characteristics, such as narrow and highly structured emission bands; large gaps between absorption and emission wavelengths (Stokes shifts); and long excited-state lifetimes, which render them suitable for highly sensitive and selective analytical methods of quantitation. Moreover, quinolones have been widely prescribed in both human and animal treatments, which has led to an increase in their impact on the environment, and therefore to a growing interest in the development of new methods for their quantitative determination. Therefore, analytical applications for the quantitative determination of quinolones, lanthanide and miscellaneous ions and nucleic acids, along with other applications, are reviewed here. Full article

(This article belongs to the Special Issue Quinolones: Chemistry and Biological Activities)

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