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Heterocyclic Molecules in Drug Discovery

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

Deadline for manuscript submissions: 30 June 2026 | Viewed by 2002

Special Issue Editor


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Guest Editor
Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, The Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland
Interests: organic synthesis; heterocycles; dipyridothiazines; structural analysis; lipophylicity; SAR
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Special Issue Information

Dear Colleagues,

Heterocyclic compounds are cyclic molecules in which one or more carbon atoms have been replaced by other heteroatoms, such as nitrogen, oxygen, sulfur, and selenium. These compounds are widely distributed in nature; above all, they are also valuable drugs. Additionally, they are used in the agrochemical industry, as disinfectants, and have been employed as corrosion inhibitors. Considering the contemporary challenges of medicine in effectively combating civilization diseases, there is an interest in heterocyclic systems in the broadly understood design of drugs.

This Special Issue, "Heterocyclic Molecules in Drug Discovery", aims to present interesting and inspiring research on the synthesis, structural analysis, delivery methods, and biotransformation of bioactive organic, heterocyclic compounds. Articles showing both new heterocyclic compounds and their structural as well as ADME properties, which are extremely important in drug design, are considered.

In addition, it is expected that the chemistry of heterocycles, in a broad sense, will also be described and discussed in the proposed review articles.

I hope that the proposed Special Issue will offer an interesting view of the current scientific research using heterocyclic molecules.

Prof. Dr. Beata Morak-Młodawska
Guest Editor

Manuscript Submission Information

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Keywords

  • organic synthesis of bioactive heterocyclic compounds
  • structural analysis of heterocycles
  • biological activity of heterocycles
  • ADME properties of heterocycles
  • in silico analysis and experimental analysis of heterocyclic molecules

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Published Papers (2 papers)

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Research

11 pages, 1734 KB  
Article
Click Chemistry-Enabled Parallel Synthesis of N-Acyl Sulfonamides and Their Evaluation as Carbonic Anhydrase Inhibitors
by Oleksii V. Gavrylenko, Bohdan V. Vashchenko, Vasyl Naumchyk, Bohdan S. Sosunovych, Oleksii Chuk, Oleksii Hrabovskyi, Olga Kuchuk, Alla Pogribna, Sergiy O. Nikitin, Anzhelika I. Konovets, Volodymyr S. Brovarets, Sergey A. Zozulya, Dmytro S. Radchenko, Oleksandr O. Grygorenko and Yurii S. Moroz
Molecules 2026, 31(2), 318; https://doi.org/10.3390/molecules31020318 - 16 Jan 2026
Viewed by 801
Abstract
A synthetically accessible library of N-acyl sulfonamides was constructed using a combination of copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) and N-acylation of primary sulfonamides. The proposed two-step reaction sequence had a high experimentally confirmed synthetic success rate (up to 85%) and gave reasonable [...] Read more.
A synthetically accessible library of N-acyl sulfonamides was constructed using a combination of copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) and N-acylation of primary sulfonamides. The proposed two-step reaction sequence had a high experimentally confirmed synthetic success rate (up to 85%) and gave reasonable product yields (up to 61%). As a result of the validation process, a 262-member compound library (out of >70K accessible combinations) was prepared. Biological profiling of the synthesized library by differential scanning fluorimetry and enzymatic assays identified several low micromolar inhibitors of human carbonic anhydrase. The interaction of the discovered hits with the biological target was studied by docking and molecular dynamics. Full article
(This article belongs to the Special Issue Heterocyclic Molecules in Drug Discovery)
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28 pages, 2720 KB  
Article
From Lipid Regulation to Neuroprotection: Multitarget (Benzo)thiazine Derivatives as Promising Leads
by Ariadni Tzara, Andrea Andreou and Angeliki P. Kourounakis
Molecules 2025, 30(23), 4542; https://doi.org/10.3390/molecules30234542 - 25 Nov 2025
Viewed by 759
Abstract
Neurodegenerative and cardiovascular disorders share multifactorial origins, including oxidative stress, (neuro)inflammation, and lipid dysregulation—factors often addressed independently by single-target therapies. In this study, we report a rational multitarget approach through the design and synthesis of novel (benzo)thiazine derivatives that integrate antioxidant, anti-inflammatory, and [...] Read more.
Neurodegenerative and cardiovascular disorders share multifactorial origins, including oxidative stress, (neuro)inflammation, and lipid dysregulation—factors often addressed independently by single-target therapies. In this study, we report a rational multitarget approach through the design and synthesis of novel (benzo)thiazine derivatives that integrate antioxidant, anti-inflammatory, and antihyperlipidemic functionalities within a single molecular framework. The compounds were obtained in good yields via 3–7 step synthetic routes and evaluated through complementary in vitro and in vivo assays. Several derivatives displayed potent inhibition of lipoxygenase (IC50 < 100 μM), significant reduction in carrageenan-induced edema (up to 60%), strong free radical scavenging and lipid peroxidation inhibition, as well as effective iron chelation. In vivo, most derivatives enhanced total antioxidant capacity (by 50–800%) and significantly improved plasma lipid profiles in mouse, while almost all compounds increased the plasma antiatherogenic index by more than 100% with selected compounds exceeding 600%. Notably, several molecules also showed moderate acetylcholinesterase inhibition, suggesting preliminary neuroprotective potential. Altogether, these multifunctional (benzo)thiazine derivatives represent promising lead structures for the development of agents targeting the complex interplay of oxidative, inflammatory, and metabolic pathways underlying neurodegenerative and cardiovascular diseases. Full article
(This article belongs to the Special Issue Heterocyclic Molecules in Drug Discovery)
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