Cover image for Vol. 11 Issue 14

Editorial Board Chairs: Antonello Mai, Rainer Metternich. Assoc. Editors: David Peralta, Scott Williams (Sr)

Impact Factor: 2.98

ISI Journal Citation Reports © Ranking: 2015: 18/59 (Chemistry Medicinal); 76/253 (Pharmacology & Pharmacy)

Online ISSN: 1860-7187

Associated Title(s): Angewandte Chemie International Edition, Chemistry - A European Journal, Chemistry – An Asian Journal, ChemBioChem, Medicinal Research Reviews, Molecular Informatics

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July 24, 2016

Drugs to Fight Bugs

Drugs to Fight BugsTwo recent reports in ChemMedChem are making waves in antimicrobial research. In the early July issue (13), professors William Wuest (Temple University), Kevin Minbiole (Villanova University), and co-workers report branched tetracationic quaternary ammonium compounds (QACs) as the most potent QACs reported so far against methicillin-resistant S. aureus. Their work is a significant breakthrough in the field of antiseptics and anti-biofilm agents.

In the current issue (14), Prof. R. D. Süssmuth and colleagues at the Technische Universität Berlin report their study of highly potent albicidin derivatives which will aid in the development of more drug-like structures of this class of antibiotic.

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Recently Published Articles

  1. Structure, Function, and Inhibition of Staphylococcus aureus Heptaprenyl Diphosphate Synthase

    Janish Desai, Dr. Yi-Liang Liu, Hongli Wei, Dr. Weidong Liu, Dr. Tzu-Ping Ko, Prof. Rey-Ting Guo and Prof. Eric Oldfield

    Version of Record online: 26 JUL 2016 | DOI: 10.1002/cmdc.201600311

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    New drug target: Staphylococcus aureus heptaprenyl diphosphate synthase (HepPPS), involved in menaquinone biosynthesis, functions as a heterodimer and is inhibited by bisphosphonates (IC50=0.83 μm), which also inhibit S. aureus cell growth, an effect that is rescued by menaquinone. HepPPS is also partially inhibited by its substrates FPP as well as IPP, most likely due to disruption of the heterodimeric complex structure.

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    Chemical Platform for the Preparation of Synthetic Orally Active Peptidomimetics with Hemoregulating Activity

    Prof. Vladislav Deigin, Dr. Olga Ksenofontova, Dr. Alexey Khrushchev, Dr. Oleg Yatskin, Dr. Alexandra Goryacheva and Prof. Vadim Ivanov

    Version of Record online: 26 JUL 2016 | DOI: 10.1002/cmdc.201600157

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    Robust and bioavailable! The low stability of peptide pharmaceuticals in non-invasive administration limits the use of these compounds in medical practice. We developed a platform based on branched piperazine-2,5-diones for creating orally stable peptidomimetics. These derivatives were attached to the N or C termini of an active linear peptide, increasing their resistance against proteolytic activity. As a result, the first orally active hemostimulatory peptides have been prepared.

  3. Multicomponent Petasis-borono Mannich Preparation of Alkylaminophenols and Antimicrobial Activity Studies

    Íris Neto, Joana Andrade, Prof. A. S. Fernandes, Catarina Pinto Reis, Jagadish K. Salunke, Prof. Arri Priimagi, Prof. Nuno R. Candeias and Prof. Patrícia Rijo

    Version of Record online: 26 JUL 2016 | DOI: 10.1002/cmdc.201600244

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    Antibiotics by MCR: We disclose a new family of antibacterial agents derived from para-nitrophenols and indoline, prepared by a multicomponent reaction (MCR). The new alkylaminophenols show minimum inhibitory concentrations lower than 1.4 μm against selected resistant microorganisms. Cytotoxicity assays demonstrated that such compounds are viable candidates as antibacterials, as no cytotoxicity was observed at these concentrations.

  4. Dioxonaphthoimidazoliums are Potent and Selective Rogue Stem Cell Clearing Agents with SOX2-Suppressing Properties

    Dr. Si-Han Sherman Ho, Dr. Azhar Ali, Yi-Cheng Ng, Dr. Kuen-Kuen Millie Lam, Prof. Shu Wang, Prof. Woon-Khiong Chan, Dr. Tan-Min Chin and Prof. Mei-Lin Go

    Version of Record online: 22 JUL 2016 | DOI: 10.1002/cmdc.201600262

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    Removing the rogues: The safety of stem cell therapy depends on the removal of undifferentiated rogue cells, which would otherwise transform into a malignant phenotype. The potent and selective stemotoxic properties of dioxonaphthoimidazoliums highlight their potential as stem cell clearing agents that could be deployed for this purpose.

  5. Synthesis of Albicidin Derivatives: Assessing the Role of N-terminal Acylation on the Antibacterial Activity

    Dennis Kerwat, Stefan Grätz, Dr. Julian Kretz, Maria Seidel, Maria Kunert, Dr. John B. Weston and Prof. Dr. Roderich D. Süssmuth

    Version of Record online: 21 JUL 2016 | DOI: 10.1002/cmdc.201600231

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    Advantages of acylated albicidin: The peptide antibiotic albicidin represents the most prominent member of a new class of antibacterial gyrase inhibitors. It shows remarkable antibacterial activities against Gram-positive and Gram-negative microorganisms. 14 newly synthesized albicidin derivatives with structural variations at the N-terminus are reported here. Gyrase inhibition and determination of minimal inhibitorial concentrations were assessed in parallel to show activities in a nm range and the necessity of N-acylation.