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3. Targeting antibiotic resistance

Author

Chellat, Mathieu F., Raguž, Luka, Riedl, Rainer, Chellat, Mathieu F., Raguž, Luka, and Riedl, Rainer

Abstract

Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human-pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even lastresort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled “Combat drug resistance: no action today means no cure tomorrow” triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens.

Published
2018

4. Pseudouridimycin : das erste Nukleosid-Analogon, das bakterielle RNA-Polymerase selektiv inhibiert

Author

Chellat, Mathieu F., Riedl, Rainer, Chellat, Mathieu F., and Riedl, Rainer

Abstract

Gesucht und gefunden: Nach Jahren der Fokussierung auf synthetische Antibiotika konnte jetzt ein neuartiger antibiotischer Wirkstoff durch konventionelles Screening in mikrobiellen Naturstoffextrakten entdeckt werden: Pseudouridimycin (PUM). Der selektive Nukleosid-Analogon-basierte Inhibitor der bakteriellen RNA-Polymerase zeigt ein breites Wirkspektrum und eine geringe Resistenzrate.

Published
2018

5. Pseudouridimycin : the first nucleoside analogue that selectively inhibits bacterial RNA polymerase

Author

Chellat, Mathieu F., Riedl, Rainer, Chellat, Mathieu F., and Riedl, Rainer

Abstract

Seek, and ye shall find: After years of focusing research on synthetic antibiotics out of fear that all the useful natural ones had already been found, a novel antibacterial compound has been discovered through conventional microbial extract screening. The broad-spectrum nucleoside-analogue inhibitor pseudouridimycin is selective for bacterial RNA polymerase and elicits very low resistance rates.

Published
2018

6. Antibiotikaresistenzen gezielt überwinden

Author

Chellat, Mathieu F., Raguž, Luka, Riedl, Rainer, Chellat, Mathieu F., Raguž, Luka, and Riedl, Rainer

Abstract

Neue Strategien zur Bekämpfung von Antibiotikaresistenzen zu finden, ist eine der grössten globalen Herausforderungen für die Gesundheitssysteme. In den letzten Jahrzehnten gab es eine drastische Zunahme an humanpathogenen Bakterien, die resistent gegen Antibiotika sind. Immer mehr Infektionen, die durch resistente Mikroorganismen verursacht werden, lassen sich nicht mehr mit konventionellen Behandlungen kurieren, und selbst Reserveantibiotika verlieren ihre Wirkung. Zusätzlich sind die Entwicklungsströme an neuen Antibiotika aus der pharmazeutischen Industrie in den letzten Jahrzehnten versiegt. Die Weltgesundheitsorganisation hat mit ihrem Aufruf „Combat drug resistance: no action today means no cure tomorrow“ eine Zunahme der Forschungsaktivitäten auf diesem Gebiet stimuliert, und mehrere neue,vielversprechende Strategien zur Wiederherstellung antibiotischer Behandlungsoptionen konnten seitdem entwickelt werden.

Published
2018

7. Targeting antibiotic resistance

Author

Chellat, Mathieu F., Raguž, Luka, and Riedl, Rainer

Subjects
0301 basic medicine, medicine.medical_specialty, medicine.drug_class, Antibiotic resistance, 030106 microbiology, Antibiotics, Reviews, Medicinal chemistry, Review, Drug resistance, Molecular Dynamics Simulation, Pharmacology, antibiotics, Catalysis, World health, Drug design, Structure-Activity Relationship, 03 medical and health sciences, 615: Pharmakologie und Therapeutik, Bacterial Proteins, Drug Resistance, Multiple, Bacterial, medicine, Intensive care medicine, Oxazoles, Oxazolidinones, Bacteria, business.industry, Public health, Conventional treatment, Treatment options, General Chemistry, Organophosphates, Anti-Bacterial Agents, 540: Chemie, structure–activity relationships, Macrolides, business
Abstract

Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human‐pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last‐resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled “Combat drug resistance: no action today means no cure tomorrow” triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens.

Published
2016
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13. Organocatalytic Asymmetric Annulation of 1,3-Bis(alkoxycarbonyl)buta-1,3-dienes and Aldehydes

Author

Pezzati, Bernardo, Chellat, Mathieu F., Murphy, John J., Besnard, Céline, Reginato, Gianna, Stephens, John C., Alexakis, Alexandre, Pezzati, Bernardo, Chellat, Mathieu F., Murphy, John J., Besnard, Céline, Reginato, Gianna, Stephens, John C., and Alexakis, Alexandre

Abstract

Asymmetric organocatalytic annulation of E/Z isomeric mixtures of bis(alkyl carboxylate)buta-1,3-dienes and aldehydes has been realized via enamine catalysis. In the presence of R,R-diphenyl-2-pyrrolidinemethanol trimethylsilyl ether, excellent stereo- and enantioselectivities were achieved for a broad spectrum of substrates.

Published
2013

17. Mechanistic Insight into the Halogen Dance Rearrangement of Iodooxazoles.

Author

Proust, Nicolas, Chellat, Mathieu F., and Stambuli, James P.

Subjects
*HALOGEN compounds, *HETEROCYCLIC compounds, *CATALYSIS, *OXAZOLES, *HALIDES, *CHEMICAL reactions
Abstract

The lithium diisopropylamide mediated halogen dance reaction of 5-iodooxazoles to generate 4-iodooxazoles was studied. The mechanism of the reaction was investigated and compared to the reported mechanism for the halogen dance rearrangement of 5- bromooxazoles. Reaction conditions were optimized and yields of iodooxazole were improved to a synthetically useful level. The use of 2-(butylsulfanyl)-5-bromooxazole as an organic catalyst turned out to be the cornerstone for the success of this reaction. [ABSTRACT FROM AUTHOR]

Published
2011
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18. A Structural View on Medicinal Chemistry Strategies against Drug Resistance.

Author

Agnello S, Brand M, Chellat MF, Gazzola S, and Riedl R

Subjects
Animals, Anti-HIV Agents pharmacology, Anti-Infective Agents pharmacology, Antimalarials pharmacology, Antineoplastic Agents pharmacology, Drug Design, Humans, Models, Molecular, Molecular Structure, Protein Binding, Signal Transduction, Structure-Activity Relationship, Anti-HIV Agents chemistry, Anti-Infective Agents chemistry, Antimalarials chemistry, Antineoplastic Agents chemistry, Drug Resistance drug effects
Abstract

The natural phenomenon of drug resistance is a widespread issue that hampers the performance of drugs in many major clinical indications. Antibacterial and antifungal drugs are affected, as well as compounds for the treatment of cancer, viral infections, or parasitic diseases. Despite the very diverse set of biological targets and organisms involved in the development of drug resistance, the underlying molecular mechanisms have been identified to understand the emergence of resistance and to overcome this detrimental process. Detailed structural information on the root causes for drug resistance is nowadays frequently available, so next-generation drugs can be designed that are anticipated to suffer less from resistance. This knowledge-based approach is essential for fighting the inevitable occurrence of drug resistance., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2019
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19. Pseudouridimycin: The First Nucleoside Analogue That Selectively Inhibits Bacterial RNA Polymerase.

Author

Chellat MF and Riedl R

Subjects
Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Bacterial Proteins antagonists & inhibitors, DNA-Directed RNA Polymerases antagonists & inhibitors, Gram-Negative Bacteria drug effects, Nucleosides chemistry, Nucleosides metabolism, Nucleosides pharmacology, Structure-Activity Relationship, Anti-Bacterial Agents metabolism, Bacteria enzymology, Bacterial Proteins metabolism, DNA-Directed RNA Polymerases metabolism, Nucleosides analogs & derivatives
Abstract

Seek, and ye shall find: After years of focusing research on synthetic antibiotics out of fear that all the useful natural ones had already been found, a novel antibacterial compound has been discovered through conventional microbial extract screening. The broad-spectrum nucleoside-analogue inhibitor pseudouridimycin is selective for bacterial RNA polymerase and elicits very low resistance rates., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2017
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20. Targeting Antibiotic Resistance.

Author

Chellat MF, Raguž L, and Riedl R

Subjects
Anti-Bacterial Agents chemistry, Bacteria metabolism, Bacterial Proteins antagonists & inhibitors, Bacterial Proteins biosynthesis, Drug Design, Macrolides chemistry, Macrolides pharmacology, Molecular Dynamics Simulation, Organophosphates chemistry, Organophosphates pharmacology, Oxazoles chemistry, Oxazoles pharmacology, Oxazolidinones chemistry, Oxazolidinones pharmacology, Structure-Activity Relationship, Anti-Bacterial Agents pharmacology, Drug Resistance, Multiple, Bacterial drug effects
Abstract

Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human-pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last-resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled "Combat drug resistance: no action today means no cure tomorrow" triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens., (© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Published
2016
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