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Synthesis of Heterocyclic Compounds via Cycloadditions: Applications in Medicinal Chemistry

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

Deadline for manuscript submissions: 20 May 2024 | Viewed by 2098

Special Issue Editors

Department of Chemistry, Indiana University, Bloomington, IN 47405, USA
Interests: flow chemistry; organic synthesis; total synthesis; cycloadditions; heterocyclics; carbohydrates; medicinal chemistry
Special Issues, Collections and Topics in MDPI journals
School of Chemistry, University of KwaZulu-Natal, Durban, South Africa
Interests: synthetic methodology; computational chemistry and molecular modelling; pharmacophore design; medicinal Chemistry; ligand–protein interactions; peptide folding; docking
Special Issues, Collections and Topics in MDPI journals
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
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Heterocyclic compounds, also known as heterocycles, are the most common constituents of many pharmaceutical drugs. They are the major class of organic chemical compounds characterized by the notion that some or all of the atoms are joined in rings containing at least one atom other than carbon. Heterocyclic compounds are used in agrochemicals and pharmaceutical industries. They are used as starting materials in the synthesis of organic compounds and used in corrosion inhibitors, sanitizers, antiordinates, developers, pesticides, dyes and plastics.

The hybridization of two heterocyclic scaffolds forms a single compound, with the potential to have antibacterial, antimalarial, antitubercular and anticancer activity. Active functional groups like hydroxyl, methyl, carbonyl, carboxyl, amino, phosphate, etc., are often used in the synthetic strategy to join the two scaffolds together. Further, heterocycles including beta-lactams, pyrimidinones, 1,3,4-thiadiazoles and their molecular hybrids with different pharmacophoric assemblies following the hetero Diels–Alder methodology are known for their biological activities under in vitro conditions. Understanding how the rings of this class of antibiotics are formed is crucial to developing new treatments to combat antibiotic resistance using cycloadditions.

Cycloaddition reactions are considered among the most powerful bond-forming reactions in organic synthesis because of their ability to form many bonds in one step and the potential to generate several stereogenic centers at the same time with predictable stereochemical outcomes. Cycloaddition reactions are applied to the synthesis of anticancer compounds by making use of classical Diels–Alder and their hetero version for the design and synthesis of compounds that were tested for their antiproliferative activities as well as apoptosis. 1,3-dipolar cycloaddition reactions of selected 1,3-dipoles, such as azides, nitrones, nitrile oxides, nitrile imines and azomethine ylides, also have a major application in the preparation of key intermediates for anticancer synthesis. In addition, the products obtained from the pericyclic reaction approaches are important for anticancer activities and the relevant biological data are highlighted.

Medicinal chemistry remains the most valuable science and plays the most critical role in the drug-development process. It acts as the backbone of the drug-discovery framework that provides a comprehensive understanding of the underlying principles of drug action and behavior within the body, which is fundamental to today's pharmaceutical care and patient counseling.

This Special Issue targets the public understanding of the chemistry behind heterocycles for pharmaceutical applications. Preference will be given to articles, which focus on target-based design strategies, organic synthesis, in vitro assays, enzymatic assays that confirm the target, in vivo experiments, SAR, and docking that improves the understanding of drug design and action. The targets are including but are not limited to: Kinases, DNA topoisomerases, Tubulin, and HDAC.

Dr. Lalitha Gummidi
Dr. Parvesh Singh
Prof. Dr. Beata Morak-Młodawska
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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

  • heterocycles
  • synthesis
  • anticancer
  • in vitro
  • cycloadditions
  • drug

Published Papers (2 papers)

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Research

13 pages, 2370 KiB  
Article
In Silico and In Vitro Studies of 4-Hydroxycoumarin-Based Heterocyclic Enamines as Potential Anti-Tumor Agents
Molecules 2023, 28(15), 5828; https://doi.org/10.3390/molecules28155828 - 02 Aug 2023
Cited by 1 | Viewed by 808
Abstract
The present study reports the one-step synthesis of several 3-formyl-4-hydroxycouramin-derived enamines (4a4i) in good yields (65–94%). The characterization of the synthesized compounds was carried out via advanced analytical and spectroscopic techniques, such as melting point, electron impact mass spectrometry [...] Read more.
The present study reports the one-step synthesis of several 3-formyl-4-hydroxycouramin-derived enamines (4a4i) in good yields (65–94%). The characterization of the synthesized compounds was carried out via advanced analytical and spectroscopic techniques, such as melting point, electron impact mass spectrometry (EI-MS), 1H-NMR, 13C-NMR, elemental analysis, FTIR, and UV-Visible spectroscopy. The reaction conditions were optimized, and the maximum yield was obtained at 3–4 h of reflux of the reactants, using 2-butanol as a solvent. The potato disc tumor assay was used to assess Agrobacterium tumefaciens-induced tumors to evaluate the anti-tumor activities of compounds (4a4i), using Vinblastine as a standard drug. The compound 4g showed the lowest IC50 value (1.12 ± 0.2), which is even better than standard Vinblastine (IC50 7.5 ± 0.6). For further insight into their drug actions, an in silico docking of the compounds was also carried out against the CDK-8 protein. The binding energy values of compounds were found to agree with the experimental results. The compounds 4g and 4h showed the best affinities toward protein, with a binding energy value of −6.8 kcal/mol. Full article
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11 pages, 2336 KiB  
Article
Full Regio- and Stereoselective Protocol for the Synthesis of New Nicotinoids via Cycloaddition Processes with the Participation of Trans-Substituted Nitroethenes: Comprehensive Experimental and MEDT Study
Molecules 2023, 28(8), 3535; https://doi.org/10.3390/molecules28083535 - 17 Apr 2023
Cited by 2 | Viewed by 736
Abstract
[3 + 2] Cycloaddition reactions with the participation of Z-C-(3-pyridyl)-N-methylnitrone and series of E-2-R-nitroethenes were both experimentally and theoretically explored in the framework of Molecular Electron Density Theory. It was found that all considered processes are realized under mild [...] Read more.
[3 + 2] Cycloaddition reactions with the participation of Z-C-(3-pyridyl)-N-methylnitrone and series of E-2-R-nitroethenes were both experimentally and theoretically explored in the framework of Molecular Electron Density Theory. It was found that all considered processes are realized under mild conditions and in full regio- and stereocontrol. The ELF analysis additionally showed that the studied reaction proceeds by a two-stage, one-step mechanism. Full article
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