Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Editor-in-Chief: Natalia Ortúzar
Impact Factor: 3.046
ISI Journal Citation Reports © Ranking: 2013: 18/58 (Chemistry Medicinal); 75/256 (Pharmacology & Pharmacy)
Online ISSN: 1860-7187
January 22, 2015
Editor's Picks: Issue 02/2015
Editor's picks for issue 02: A Communication by Denny, Cobb and colleagues, and a Full Paper by Champy and co-workers report the latest discoveries for combating two different forms of leishmaniasis. Read more...
Recently Published Articles
- Design, Synthesis, and Biological Evaluation of Simplified Side Chain Hybrids of the Potent Actin Binding Polyketides Rhizopodin and Bistramide
Daniel Herkommer, Dr. Sandra Dreisigacker, Dr. Galina Sergeev, Dr. Florenz Sasse, Prof. Dr. Holger Gohlke and Prof. Dr. Dirk Menche
Article first published online: 29 JAN 2015 | DOI: 10.1002/cmdc.201402508
Less talk, more actin: X-ray-structure-based in silico studies of the noncovalent interactions between complex polyketides and their natural target actin resulted in the design, modular synthesis, and biological evaluation of a novel and structurally simplified analogue class based on a hybrid structure of bistramide A and rhizopodin.
- On the Metabolically Active Form of Metaglidasen: Improved Synthesis and Investigation of Its Peculiar Activity on Peroxisome Proliferator-Activated Receptors and Skeletal Muscles
Dr. Antonio Laghezza, Dr. Roberta Montanari, Prof. Antonio Lavecchia, Dr. Luca Piemontese, Dr. Giorgio Pochetti, Prof. Vito Iacobazzi, Dr. Vittoria Infantino, Dr. Davide Capelli, Dr. Michela De Bellis, Dr. Antonella Liantonio, Dr. Sabata Pierno, Prof. Paolo Tortorella, Prof. Diana Conte Camerino and Prof. Fulvio Loiodice
Article first published online: 29 JAN 2015 | DOI: 10.1002/cmdc.201402462
Unexpected activity: The metabolically active forms of the selective PPARγ modulator metaglidasen and its enantiomer were carefully investigated toward PPARα. Unexpectedly, the former showed antagonist activity, whereas the latter behaved as a partial agonist. Crystallographic studies on PPARγ were performed to gain more insight on molecular-level interactions. Both stereoisomers also showed blocking activity on skeletal muscle chloride conductance.
- Preclinical Characterization of Acyl Sulfonimidamides: Potential Carboxylic Acid Bioisosteres with Tunable Properties
Dr. Sanjay R. Borhade, Dr. Richard Svensson, Dr. Peter Brandt, Prof. Dr. Per Artursson, Prof. Dr. Per I. Arvidsson and Dr. Anja Sandström
Article first published online: 28 JAN 2015 | DOI: 10.1002/cmdc.201402497
Carboxylic acid bioisosteres: A series of linear acyl sulfonimidamides were synthesized and evaluated for their in vitro physicochemical and ADME properties such as pKa, lipophilicity, metabolic stability, plasma protein binding, Caco-2 permeability, and aqueous solubility. These compounds are less acidic than carboxylic acid and showed excellent cell permeability, high solubility, and minor intestinal efflux.
- Evaluation of tert-Butyl Isosteres: Case Studies of Physicochemical and Pharmacokinetic Properties, Efficacies, and Activities
Matthias V. Westphal, Bernd T. Wolfstädter, Dr. Jean-Marc Plancher, Dr. John Gatfield and Prof. Erick M. Carreira
Article first published online: 28 JAN 2015 | DOI: 10.1002/cmdc.201402502
The alternative scene: Given how common the tert-butyl group is in medicinal chemistry, we set out to explore some isosteric alternatives in hopes of identifying motifs that circumvent the common drawbacks imparted by tert-butyl groups, such as increased lipophilicity and lower metabolic stability.
- Synthesis and Biological Evaluation of Ferrocenylquinoline as a Potential Antileishmanial Agent
Md Yousuf, Debarati Mukherjee, Abhishek Pal, Somaditya Dey, Supratim Mandal, Dr. Chiranjib Pal and Dr. Susanta Adhikari
Article first published online: 23 JAN 2015 | DOI: 10.1002/cmdc.201402537
Ironing out leishmaniasis! Ferrocenylquinoline is a unique metallocene drug candidate that exhibits promising activity against Leismania donovani promastigotes (IC50: 15.26 μM) without cytotoxicity against host splenocytes. Treatment with this compound generated substantial amounts of reactive oxygen species followed by a depletion of reduced glutathione (GSH) and loss of membrane potential, leading to cell death. It inhibits intracellular amastigotes and also increases the levels of nitric oxide in infected macrophages.