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Quinoline System in Design and Synthesis of New Bioactive Agents

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

Deadline for manuscript submissions: 15 September 2026 | Viewed by 642

Special Issue Editor


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Guest Editor
Department of Organic Chemistry, School of Pharmacy and the Division of Laboratory Medicine, Medical University of Silesia in Katowice, Sosnowiec, Poland
Interests: quinoline; heterocycle; medicinal chemistry; organic synthesis

Special Issue Information

Dear Colleagues,

The quinoline system occupies a special, privileged place in medicinal chemistry. Quinoline derivatives of both natural and synthetic origin exhibit a broad spectrum of biological activity. They possess anticancer, antimalarial, anti-inflammatory, antibacterial, antiviral, antituberculosis, and analgesic properties. Quinoline-based compounds form important scaffolds in medicinal chemistry, primarily used for the design of anti-infective and anticancer drugs. One strategy used in the design of new drugs is the creation of hybrid systems combining two biologically active molecules. This approach can be an alternative to the combined use of two or more drugs, has a beneficial effect on the pharmacokinetic parameters of the compounds (improved bioavailability), and enables their action at the appropriate target site. Research into the synthesis of hybrid systems containing a quinoline structural fragment (8-hydroxyquinoline, 4-aminoquinoline, 4-quinolone system) and other pharmacophoric systems (drug structural fragments, other heterocyclic systems) is of great importance in the design of new biologically active compounds (potential drugs).

This Special Issue of the journal "Molecules", titled "Quinoline System in Design and Synthesis of New Bioactive Agents", is devoted to the following research topics: (1) synthesis and analysis; (2) natural quinoline derivatives; (3) drug design; (4) biological studies; (5) structure-activity relationship (SAR); (6) in silico studies.

Prof. Dr. Andrzej Zięba
Guest Editor

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Keywords

  • quinoline derivatives
  • synthesis
  • analysis
  • biological activity
  • ADMET
  • SAR
  • hybrid systems
  • pharmacophore substituents
  • medicinal chemistry

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Published Papers (1 paper)

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Research

23 pages, 4855 KB  
Article
Cholinesterase Inhibitory Activity of Alkylated Quinobenzothiazinium Salts
by Sarka Stepankova, Andrzej Bak, Malgorzata Latocha, Violetta Kozik, Agata Kawulok, Josef Jampilek and Andrzej Zieba
Molecules 2026, 31(8), 1346; https://doi.org/10.3390/molecules31081346 - 19 Apr 2026
Viewed by 419
Abstract
Ten substituted quinobenzothiazinium salts were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). All the compounds inhibited AChE in the IC50 range of 0.03–0.658 µM, with 5,8,10-trimethyl-12H-quinolino[3,4-b][1,4]benzothiazin-5-ium chloride (3d) being the most potent [...] Read more.
Ten substituted quinobenzothiazinium salts were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). All the compounds inhibited AChE in the IC50 range of 0.03–0.658 µM, with 5,8,10-trimethyl-12H-quinolino[3,4-b][1,4]benzothiazin-5-ium chloride (3d) being the most potent inhibitor, with an IC50 value significantly better than that of the clinically used rivastigmine and galantamine and comparable to that of tacrine and donepezil. The IC50 values for BChE inhibition ranged from 0.34 to 4.25 µM; 5,9-dimethyl-12H-quinolino[3,4-b][1,4]benzothiazin-5-ium chloride (3b) exhibited the strongest BChE inhibitory activity and in general, all the investigated compounds were more potent inhibitors than rivastigmine and galantamine. Based on the calculated selectivity index values, they are rather preferential inhibitors of AChE. Cytotoxicity tests performed on normal human dermal fibroblasts (HFF-1) did not demonstrate any significant cytotoxicity under the tested conditions. The distance-oriented structure distribution for the studied molecules was related with the activity data using principal component analysis and hierarchical clustering analysis. (SAR)-based evaluation is reported to predict activity cliffs using a similarity–activity landscape index for the AChE inhibitory response values. Moreover, direct protein-mediated in silico methods were utilized to identify factors that may be relevant for quantitative (Q)SAR modeling. In practice, target-oriented molecular docking was used to organize the spatial distribution of the ligand property space for the anti-AChE system. In general, this series of alkylated quinobenzothiazinium salts with potent inhibitory activity against cholinesterases fulfills Lipinski’s rule of five based on in silico predictions and is also expected to have high absorption in the human gastrointestinal tract. All active derivatives are also expected to penetrate the blood–brain barrier, making them promising compounds for further research and possible use in Alzheimer’s disease therapy. Full article
(This article belongs to the Special Issue Quinoline System in Design and Synthesis of New Bioactive Agents)
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