Special Issue "Recent Contributions in Medicinal Chemistry Within European GP2A Network"

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (30 November 2019).

Special Issue Editors

Prof. Dr. Pascal Marchand
Website
Guest Editor
Université de Nantes, Cibles et médicaments des infections et du cancer, IICiMed, EA 1155, F-44000 Nantes, France
Interests: design; synthesis and biological evaluation of heterocyclic compounds for therapeutic purposes (mycology, parasitology, and cancer); inhibitors of kinase signaling pathways; ADMET properties of molecules of biological interest
Special Issues and Collections in MDPI journals
Prof. Dr. Thierry Besson
Website
Guest Editor
Normandie Univ, UNIROUEN, INSA Rouen, CNRS, COBRA UMR 6014, F-76000 Rouen, France
Interests: chemistry of heterocyclic compounds; microwave-assisted chemistry; kinases inhibitors; green chemistry applied to bioactive compounds; Alzheimer disease; Down syndrom; cancer
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

As a joint meeting, the 26th Medicinal Chemistry Conference of GP2A and 32nd Journées Franco-Belges de Pharmacochimie took place between 13th and 15th June at Asnelles sur Mer (Normandie, France) and provided a unique opportunity to engage with a wide group of European Medicinal Chemists.
Topics included chemical tools for medicinal chemistry, protein–protein interactions, epigenetic, natural product-inspired molecules, computer-aided drug design, and new strategies for the design and development of drugs.
Speakers at the conference and other researchers are cordially invited to contribute original research papers or reviews to this Special Issue of Pharmaceuticals

Prof. Pascal Marchand
Prof. Thierry Besson
Guest Editors

Manuscript Submission Information

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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. Pharmaceuticals is an international peer-reviewed open access monthly 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 1400 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

  • medicinal chemistry
  • protein–protein interactions
  • epigenetic
  • naturel product-inspired molecules
  • computer-aided drug design

Published Papers (9 papers)

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Research

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Open AccessCommunication
Exploring Kinase Inhibition Properties of 9H-pyrimido[5,4-b]- and [4,5-b]indol-4-amine Derivatives
Pharmaceuticals 2020, 13(5), 89; https://doi.org/10.3390/ph13050089 - 09 May 2020
Abstract
We previously highlighted the interest in 6,5,6-fused tricyclic analogues of 4-aminoquinazolines as kinase inhibitors in the micromolar to the nanomolar range of IC50 values. For the generation of chemical libraries, the formamide-mediated cyclization of the cyanoamidine precursors was carried out under microwave [...] Read more.
We previously highlighted the interest in 6,5,6-fused tricyclic analogues of 4-aminoquinazolines as kinase inhibitors in the micromolar to the nanomolar range of IC50 values. For the generation of chemical libraries, the formamide-mediated cyclization of the cyanoamidine precursors was carried out under microwave irradiation in an eco-friendly approach. In order to explore more in-depth the pharmacological interest in such tricyclic skeletons, the central five member ring, i.e., thiophène or furan, was replaced by a pyrrole to afford 9H-pyrimido[5,4-b]- and [4,5-b]indol-4-amine derivatives inspired from harmine. The inhibitory potency of the final products was determined against four protein kinases (CDK5/p25, CK1δ/ε, GSK3α/β, and DYRK1A). As a result, we have identified promising compounds targeting CK1δ/ε and DYRK1A and displaying micromolar and submicromolar IC50 values. Full article
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Open AccessArticle
Structure–Activity Relationships (SARs) of α-Ketothioamides as Inhibitors of Phosphoglycerate Dehydrogenase (PHGDH)
Pharmaceuticals 2020, 13(2), 20; https://doi.org/10.3390/ph13020020 - 22 Jan 2020
Cited by 1
Abstract
For many years now, targeting deregulation within cancer cells’ metabolism has appeared as a promising strategy for the development of more specific and efficient cancer treatments. Recently, numerous reports highlighted the crucial role of the serine synthetic pathway, and particularly of the phosphoglycerate [...] Read more.
For many years now, targeting deregulation within cancer cells’ metabolism has appeared as a promising strategy for the development of more specific and efficient cancer treatments. Recently, numerous reports highlighted the crucial role of the serine synthetic pathway, and particularly of the phosphoglycerate dehydrogenase (PHGDH), the first enzyme of the pathway, to sustain cancer progression. Yet, because of very weak potencies usually in cell-based settings, the inhibitors reported so far failed to lay ground on the potential of this approach. In this paper, we report a structure–activity relationship study of a series of α-ketothioamides that we have recently identified. Interestingly, this study led to a deeper understanding of the structure–activity relationship (SAR) in this series and to the identification of new PHGDH inhibitors. The activity of the more potent compounds was confirmed by cellular thermal shift assays and in cell-based experiments. We hope that this research will eventually provide a new entry point, based on this promising chemical scaffold, for the development of therapeutic agents targeting PHGDH. Full article
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Open AccessCommunication
Biological Characterization of 8-Cyclopropyl-2-(pyridin-3-yl)thiazolo[5,4-f]quinazolin-9(8H)-one, a Promising Inhibitor of DYRK1A
Pharmaceuticals 2019, 12(4), 185; https://doi.org/10.3390/ph12040185 - 17 Dec 2019
Cited by 1
Abstract
Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) hyperactivity has been linked to the development of a number of human malignancies. DYRK1A is the most studied family member, and the discovery of novel specific inhibitors is attracting considerable interest. The 8-cyclopropyl-2(pyridin-3-yl)thiazolo[5,4-f]quinazolin-9(8H)-one (also [...] Read more.
Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) hyperactivity has been linked to the development of a number of human malignancies. DYRK1A is the most studied family member, and the discovery of novel specific inhibitors is attracting considerable interest. The 8-cyclopropyl-2(pyridin-3-yl)thiazolo[5,4-f]quinazolin-9(8H)-one (also called FC162) was found to be a promising inhibitor of DYRK1A and was characterized in biological experiments, by western transfer and flow cytometry on SH-SY5Y and pre-B cells. Here, the results obtained with FC162 are compared to well-characterized known DYRK1A inhibitors (e.g., Leucettine L41 and EHT1610). Full article
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Open AccessArticle
Biological Evaluation of Arylsemicarbazone Derivatives as Potential Anticancer Agents
Pharmaceuticals 2019, 12(4), 169; https://doi.org/10.3390/ph12040169 - 17 Nov 2019
Abstract
Fourteen arylsemicarbazone derivatives were synthesized and evaluated in order to find agents with potential anticancer activity. Cytotoxic screening was performed against K562, HL-60, MOLT-4, HEp-2, NCI-H292, HT-29 and MCF-7 tumor cell lines. Compounds 3c and 4a were active against the tested cancer cell [...] Read more.
Fourteen arylsemicarbazone derivatives were synthesized and evaluated in order to find agents with potential anticancer activity. Cytotoxic screening was performed against K562, HL-60, MOLT-4, HEp-2, NCI-H292, HT-29 and MCF-7 tumor cell lines. Compounds 3c and 4a were active against the tested cancer cell lines, being more cytotoxic for the HL-60 cell line with IC50 values of 13.08 μM and 11.38 μM, respectively. Regarding the protein kinase inhibition assay, 3c inhibited seven different kinases and 4a strongly inhibited the CK1δ/ε kinase. The studied kinases are involved in several cellular functions such as proliferation, migration, cell death and cell cycle progression. Additional analysis by flow cytometry revealed that 3c and 4a caused depolarization of the mitochondrial membrane, suggesting apoptosis mediated by the intrinsic pathway. Compound 3c induced arrest in G1 phase of the cell cycle on HL-60 cells, and in the annexin V assay approximately 50% of cells were in apoptosis at the highest concentration tested (26 μM). Compound 4a inhibited cell cycle by accumulation of abnormal postmitotic cells at G1 phase and induced DNA fragmentation at the highest concentration (22 μM). Full article
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Review

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Open AccessReview
Colchicine-Binding Site Inhibitors from Chemistry to Clinic: A Review
Pharmaceuticals 2020, 13(1), 8; https://doi.org/10.3390/ph13010008 - 03 Jan 2020
Cited by 5Correction
Abstract
It is over 50 years since the discovery of microtubules, and they have become one of the most important drug targets for anti-cancer therapies. Microtubules are predominantly composed of the protein tubulin, which contains a number of different binding sites for small-molecule drugs. [...] Read more.
It is over 50 years since the discovery of microtubules, and they have become one of the most important drug targets for anti-cancer therapies. Microtubules are predominantly composed of the protein tubulin, which contains a number of different binding sites for small-molecule drugs. There is continued interest in drug development for compounds targeting the colchicine-binding site of tubulin, termed colchicine-binding site inhibitors (CBSIs). This review highlights CBSIs discovered through diverse sources: from natural compounds, rational design, serendipitously and via high-throughput screening. We provide an update on CBSIs reported in the past three years and discuss the clinical status of CBSIs. It is likely that efforts will continue to develop CBSIs for a diverse set of cancers, and this review provides a timely update on recent developments. Full article
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Open AccessReview
A Decade of Antifungal Leads from Natural Products: 2010–2019
Pharmaceuticals 2019, 12(4), 182; https://doi.org/10.3390/ph12040182 - 12 Dec 2019
Abstract
In this review, we discuss novel natural products discovered within the last decade that are reported to have antifungal activity against pathogenic species. Nearly a hundred natural products were identified that originate from bacteria, algae, fungi, sponges, and plants. Fungi were the most [...] Read more.
In this review, we discuss novel natural products discovered within the last decade that are reported to have antifungal activity against pathogenic species. Nearly a hundred natural products were identified that originate from bacteria, algae, fungi, sponges, and plants. Fungi were the most prolific source of antifungal compounds discovered during the period of review. The structural diversity of these antifungal leads encompasses all the major classes of natural products including polyketides, shikimate metabolites, terpenoids, alkaloids, and peptides. Full article
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Other

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Open AccessCorrection
Correction: McLoughlin, E.C.; O’Boyle, N.M. Colchicine-Binding Site Inhibitors from Chemistry to Clinic: A Review. Pharmaceuticals 2020, 13, 8
Pharmaceuticals 2020, 13(4), 72; https://doi.org/10.3390/ph13040072 - 20 Apr 2020
Abstract
We, the authors, wish to make the following corrections to our paper [...] Full article
Open AccessMeeting Report
27th Annual GP2A Medicinal Chemistry Conference
Pharmaceuticals 2019, 12(4), 179; https://doi.org/10.3390/ph12040179 - 06 Dec 2019
Abstract
The 27th annual GP2A (Groupement des Pharmacochimistes de l′Arc Atlantique/Group of Medicinal Chemists in the Atlantic Arc) conference took place from 21 to 23 August 2019, at the East Midlands Conference Centre (University Park, Nottingham, United Kingdom) and was hosted by the Division [...] Read more.
The 27th annual GP2A (Groupement des Pharmacochimistes de l′Arc Atlantique/Group of Medicinal Chemists in the Atlantic Arc) conference took place from 21 to 23 August 2019, at the East Midlands Conference Centre (University Park, Nottingham, United Kingdom) and was hosted by the Division of Biomolecular Science and Medicinal Chemistry (BSMC), within the School of Pharmacy at the University of Nottingham. The event brought together an international delegation of researchers with interests in medicinal chemistry and interfacing disciplines. In addition, a pre-conference workshop provided an opportunity for younger researchers to develop their theoretical knowledge in quantitative pharmacology. Abstracts of presentations by the 14 invited speakers and 6 young researchers, in addition to 41 posters, are included in this report. Full article
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Open AccessMeeting Report
26th Annual GP2A Medicinal Chemistry Conference & 32nd Journées Franco-Belges de Pharmacochimie
Pharmaceuticals 2019, 12(2), 73; https://doi.org/10.3390/ph12020073 - 16 May 2019
Abstract
As a joint meeting, the 26th Medicinal Chemistry Conference of GP2A and 32nd Journées Franco-Belges de Pharmacochimie took place between 13th and 15th June at Asnelles sur Mer (Normandie, France), providing a unique opportunity for a wide group of European medicinal chemists to [...] Read more.
As a joint meeting, the 26th Medicinal Chemistry Conference of GP2A and 32nd Journées Franco-Belges de Pharmacochimie took place between 13th and 15th June at Asnelles sur Mer (Normandie, France), providing a unique opportunity for a wide group of European medicinal chemists to engage. Topics included chemical tools for medicinal chemistry, protein-protein interactions, epigenetics, natural product-inspired molecules, computer-aided drug design, and new strategies for the design and development of drugs. Abstracts of invited lectures, proffered young researcher communications, flash communications and posters presented during the meeting are collected in this report. Full article
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