• Issue

    ChemMedChem: Volume 17, Issue 8

    April 20, 2022

Cover Pictures

Free Access

Front Cover: Scaffold Hopping from Amodiaquine to Novel Nurr1 Agonist Chemotypes via Microscale Analogue Libraries (ChemMedChem 8/2022)

  • First Published: 20 April 2022
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The Front Cover shows a scaffold hop from amodiaquine to a new agonist of the neuroprotective transcription factor Nurr1 through library synthesis from rationally and computationally selected building blocks. The first library served to replace the diethylaminomethylphenol residue before the second set varied the chloroquinoline motif. The analogue libraries were prepared in microscale format in 1 mL glass tubes and tested for cellular Nurr1 activation after a simple workup. The most promising compounds of each library were synthesized in batch, isolated, and characterized to confirm Nurr1 agonism. Cover design by Sabine Willems. More information can be found in the Research Article by Sabine Willems, Marcel Müller, Daniel Merk et al.

Reviews

Contribution of Knoevenagel Condensation Products toward the Development of Anticancer Agents: An Updated Review

  • First Published: 28 February 2022
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Expanding on condensation: The Knoevenagel condensation is an entrenched, prevailing, prominent arsenal following greener principles in the generation of α,β-unsaturated ketones involving carbonyl functionality and active methylenes. This review compiles the efficiency of the Knoevenagel condensation to generate molecules of pharmacological interest, predominantly toward cancer.

Research Articles

Very Important Paper

Open Access

Scaffold Hopping from Amodiaquine to Novel Nurr1 Agonist Chemotypes via Microscale Analogue Libraries

  • First Published: 08 February 2022
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The nuclear receptor Nurr1 is considered a neuroprotective transcription factor and ascribed high therapeutic potential, but Nurr1 activators are rare. Using the Nurr1 agonist amodiaquine as starting point, microscale analogue libraries were synthesized and tested in a cellular setting to identify new Nurr1 ligand scaffolds. Thereby, novel synthetic Nurr1 activators exceeding amodiaquine in potency were obtained.

WaterMap-Guided Structure-Based Virtual Screening for Acetylcholinesterase Inhibitors

  • First Published: 14 February 2022
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From in silico to in vivo: Novel acetylcholinesterase inhibitors were identified in docking-based virtual screening followed by WaterMap calculations. The compounds displayed significant structural novelty relative to known acetylcholine inhibitors. The safety/toxicity of these compounds were assessed in a zebrafish model.

Synthesis of Dihydrobenzofuro[3,2-b]chromenes as Potential 3CLpro Inhibitors of SARS-CoV-2: A Molecular Docking and Molecular Dynamics Study

  • First Published: 03 February 2022
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A simple strategy was designed to synthesize dihydrobenzofuro[3,2-b]chromenes. Their potential application as inhibitors of 3CLpro of the SARS-CoV-2 virus was explored by molecular docking, dynamics simulations, and in-silico ADMET studies.

Biochemical Screening of Potent Zika Virus Protease Inhibitors

  • First Published: 01 February 2022
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Antiviral arsenal: In biochemical high-throughput screens, 10 novel inhibitors of Zika virus protease, which is essential for viral replication, were identified. All inhibitors obtained were natural products, and their Ki values ranged from 5 nM to 8 μM. These compounds could be of interest as leads for the development of important and essential Zika antiviral drugs.

Quinoline-Dihydropyrimidin-2(1H)-one Hybrids: Synthesis, Biological Activity, and Mechanistic Studies

  • First Published: 16 February 2022
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Antiplasmodial activity, in silico docking in the binding pockets of dihydrofolate reductase, heme binding, ADMET properties, and antiviral properties of a new set of quinolone-dihydropyrimidinone hybrids is presented. Compounds showed moderate to good antiplasmodial activity against chloroquine-sensitive (D10) and resistant (Dd2) strains of Plasmodium falciparum.

A Bimetallic Nanozyme with Cascade Effect for Synergistic Therapy of Cancer

  • First Published: 29 January 2022
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Anticancer catalysis: Bimetallic nanozyme (DMSN-Au-Ru NPs) integrated Au NPs and Ru NPs into the large pore channels of dendritic mesoporous silica nanoparticles could achieve synergistic effect of PTT and self-enhanced PDT. Both in vitro and in vivo experiments show the therapeutic effects of the nanocomposites.

Open Access

The Exception That Proves the Rule: How Sodium Chelation Can Alter the Charge-Cell Binding Correlation of Fluorescein-Based Multimodal Imaging Agents

  • First Published: 09 February 2022
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The exception that proves the rule: This work elucidates that the chelation of sodium by the fluorescent dye fluorescein reduces the net charge of the dye molecule and by this influences the receptor binding parameters of a fluorescein-comprising hybrid multimodal imaging agent.

Functional Disruption of Gli1-DNA Recognition via a Cobalt(III) Complex

  • First Published: 18 March 2022
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Co(III) Schiff-base complexes displace native Zn(II) ions from zinc finger transcription factors overexpressed in many types of cancer. As a result, the helical secondary structure necessary for consensus DNA sequence recognition is structurally compromised. We used a Co(III)-sb to inhibit the Gli1 zinc finger transcription factor, which is known to cause aberrant activation of the Hedgehog pathway in basal carcinoma, medulloblastoma, and pancreatic adenocarcinoma.