COVID-19: Failure of the DisCoVeRy Clinical Trial, and Now-New Hopes?

The DisCoVeRy clinical trial aimed at the evaluation of four treatments for patients suffering from severe to critical COVID-19: Hydroxychloroquine, eventually associated with azithromycin; the combination lopinavir/ritonavir; the combination with the addition of interferon β-1a; remdesivir. The trial was discontinued due to the lack of positive results. Meanwhile, many other potential options have been considered either to target the virus itself, the interactions with the host cells, or the cytokine storm frequently observed during the infection.

Dual-Target Inhibitors of the Folate Pathway Inhibit Intrinsically Trimethoprim-Resistant DfrB Dihydrofolate Reductases.

Trimethoprim (TMP) is widely used to treat infections in humans and in livestock, accelerating the incidence of TMP resistance. The emergent and largely untracked type II dihydrofolate reductases (DfrBs) are intrinsically TMP-resistant plasmid-borne Dfrs that are structurally and evolutionarily unrelated to chromosomal Dfrs. We report kinetic characterization of the known DfrB family members.

COVID-19: An Update About the Discovery Clinical Trial.

Finding efficacious and safe treatments for COVID-19 emerges as a crucial need in order to control the spread of the pandemic. Whereas plasma therapy attracts much interest, the European project Discovery focuses on the potentialities of small molecules like remdesivir, the combination of lopinavir/ritonavir, hydroxychloroquine, and chloroquine. Results recently published on the clinical evaluation of those drugs are compiled in this brief report, although complete data are still impatiently awaited.

COVID-19: A Brief Overview of the Discovery Clinical Trial.

The outbreak of COVID-19 is leading to a tremendous search for curative treatments. The urgency of the situation favors a repurposing of active drugs but not only antivirals. This short communication focuses on four treatments recommended by WHO and included in the first clinical trial of the European Discovery project.

2019: An Awesome Year for .

Ending the year is an opportunity to reflect on the past, in particular the past twelve months [...

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-6.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials that is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal [...

Bioactive Aliphatic Polycarbonates Carrying Guanidinium Functions: An Innovative Approach for Myotonic Dystrophy Type 1 Therapy.

type 1 (DM1) results from nuclear sequestration of splicing factors by a messenger RNA (mRNA) harboring a large (CUG) repeat array transcribed from the causal (CTG) DNA amplification. Several compounds were previously shown to bind the (CUG) RNA and release the splicing factors. We now investigated for the first time the interaction of an aliphatic polycarbonate carrying guanidinium functions to DM1 DNA/RNA model probes by affinity capillary electrophoresis.

Structure-Based Design of Dimeric Bisbenzimidazole Inhibitors to an Emergent Trimethoprim-Resistant Type II Dihydrofolate Reductase Guides the Design of Monomeric Analogues.

The worldwide use of the broad-spectrum antimicrobial trimethoprim (TMP) has induced the rise of TMP-resistant microorganisms. In addition to resistance-causing mutations of the microbial chromosomal dihydrofolate reductase (Dfr), the evolutionarily and structurally unrelated type II Dfrs (DfrBs) have been identified in TMP-resistant microorganisms. DfrBs are intrinsically TMP-resistant and allow bacterial proliferation when the microbial chromosomal Dfr is TMP-inhibited, making these enzymes important targets for inhibitor development.

Tafenoquine: A 2018 Novel FDA-Approved Prodrug for the Radical Cure of Malaria and Prophylaxis of Malaria.

Tafenoquine (an 8-aminoquinoline) was approved by the Food and Drug Administration (FDA) in 2018 for the radical cure of malaria and preventive action against malaria. Despite the fact that the mechanism of action of the drug remains unclear, all studies indicated that a metabolite is responsible for its efficacy. Routes for the preparation of the drug are described.

Baricitinib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Janus Kinases.

In 2018, Baricitinib was approved by the Food and Drig Administration (FDA) for the treatment of rheumatoid arthritis. Baricitinib exerts its action by targeting Janus kinases (JAK). In this study, we describe the necessary steps for preparing the drug using two alternative routes.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes⁻4.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials, which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal . [..

Correction to: Affinity capillary electrophoresis for identification of active drug candidates in myotonic dystrophy type 1.

Unfortunately the name of Jean Jacques Vanden Eynde was missing as co-author of this contribution. The correct list of authors is: Ioan O. Neaga, Stephanie Hambye, Ede Bodoki, Claudio Palmieri, Jean Jacques Vanden Eynde, Eugénie Ansseau, Alexandra Belayew, Radu Oprean, Bertrand Blankert.

2017: A Fruitful Year for Pharmaceuticals.

First of all, let me wish you a healthy and wonderful year in 2018 [...

Pharmaceuticals: Impact Factor or CiteScore™.

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Announcing the 2017 Pharmaceuticals Travel Award for Young Post-Doctoral Researchers.

Last year, for the first time in its history, our Journal was able to offer a travel grant of 800 CHF to a young researcher in the field of medicinal chemistry.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes.

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Potential of bisbenzimidazole-analogs toward metronidazole-resistant Trichomonas vaginalis isolates.

A bisoxyphenylene-bisbenzimidazole series with increasing aliphatic chain length (CH to C H ) containing a meta- (m) or para (p)-benzimidazole linkage to the phenylene ring was tested for ability to inhibit the growth of metronidazole-susceptible (C1) and metronidazole-refractory (085) Trichomonas vaginalis isolates under aerobic and anaerobic conditions. Compound 3m, 2,2'-[α,ω-propanediylbis(oxy-1,3-phenylene)]bis-1H-benzimidazole, displayed a 5.5-fold lower minimum inhibitory concentration (MIC) toward T.

Progress Confirmed for Pharmaceuticals in 2016.

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Announcing the 2016 Pharmaceuticals Travel Award for Young Investigators.

For the first time in its short history, our journal is able, this year, to support a young researcher in the field of medicinal chemistry by offering a travel grant of 800 CHF.[..

Evaluation of bisbenzamidines as inhibitors for matriptase-2.

The serine protease matriptase-2 has attracted much attention as a potential target for the treatment of iron overload diseases. In this study, a series of 27 symmetric, achiral bisbenzamidines was evaluated for inhibitory activity against human matriptase-2, against the closely related enzyme human matriptase, as well as against human thrombin, bovine factor Xa and human trypsin. The conformationally restricted piperazine derivative 19 and the oxamide-derived bisbenzamidine 1 were identified as the most potent inhibitors of this series for matriptase-2 and matriptase, respectively.

How Efficient Is My (Medicinal) Chemistry?

"Greening" a chemical transformation is not about only changing the nature of a solvent or decreasing the reaction temperature. There are metrics enabling a critical quantification of the efficiency of an experimental protocol. Some of them are applied to different sequences for the preparation of paracetamol in order to understand their performance parameters and elucidate pathways for improvement.

Alkanediamide-Linked Bisbenzamidines Are Promising Antiparasitic Agents.

A series of 15 alkanediamide-linked bisbenzamidines and related analogs was synthesized and tested in vitro against two Trypanosoma brucei (T.b.) subspecies: T.

2015: A Transition Year for Pharmaceuticals?

In this period, I could not start this editorial without wishing all of you a Happy New Year. This is also the opportunity for me to warmly thank, for their confidence, our authors, readers, reviewers, members of the editorial board, sponsors, as well as members of MDPI AG in Basel, Beijing, and Wuhan. [.