Design, synthesis and evaluation of novel polypharmacological antichlamydial agents

Sunduru, Naresh; Salin, Olli; Gylfe, Åsa; Elofsson, Mikael

doi:10.1016/j.ejmech.2015.07.019

Cited by 15 publications

(16 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[222][223][224] Salicylidene acylhydrazides (SAHs) represent aw ell-known class of T3SS inhibitors that have been extensively studied in various pathogens including P. aeruginosa and Salmonella typhimurium. [225][226][227][228][229] However, these SAHs seem to function through several mechanisms which need further elucidation. [225][226][227][228][229] However, these SAHs seem to function through several mechanisms which need further elucidation.…”

Section: Type III Secretion Systems (T3ss)mentioning

confidence: 99%

“…[224] Diverse SAH derivatives such as INP0341 have been synthesized and were found to attenuate bacterial pathogenesis. [225][226][227][228][229] However, these SAHs seem to function through several mechanisms which need further elucidation. [230] In ad ifferent approach, screening of compound libraries with acellular reporter assay revealed phenoxyacetamide MBX 1641 to be ap otent inhibitor of P. aeruginosa T3SS (IC 50 % 10 mm)w ith al ow toxicity against eukaryotic cells ( Figure 16).…”

Section: Type III Secretion Systems (T3ss)mentioning

confidence: 99%

See 1 more Smart Citation

Thinking Outside the Box—Novel Antibacterials To Tackle the Resistance Crisis

et al. 2018

View full text Add to dashboard Cite

The public view on antibiotics as reliable medicines changed when reports about "resistant superbugs" appeared in the news. While reasons for this resistance development are easily spotted, solutions for re-establishing effective antibiotics are still in their infancy. This Review encompasses several aspects of the antibiotic development pipeline from very early strategies to mature drugs. An interdisciplinary overview is given of methods suitable for mining novel antibiotics and strategies discussed to unravel their modes of action. Select examples of antibiotics recently identified by using these platforms not only illustrate the efficiency of these measures, but also highlight promising clinical candidates with therapeutic potential. Furthermore, the concept of molecules that disarm pathogens by addressing gatekeepers of virulence will be covered. The Review concludes with an evaluation of antibacterials currently in clinical development. Overall, this Review aims to connect select innovative antimicrobial approaches to stimulate interdisciplinary partnerships between chemists from academia and industry.

show abstract

Section: Type III Secretion Systems (T3ss)mentioning

confidence: 99%

Section: Type III Secretion Systems (T3ss)mentioning

confidence: 99%

Thinking Outside the Box—Novel Antibacterials To Tackle the Resistance Crisis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…[221] Es wurde eine Reihe von T3SS-Inhibitoren entdeckt, welche die Regulation der Expression des T3SS,d ie Synthese der nadelartigen Struktur sowie die Sekretion und Tr anslokation von Effektorproteinen beeinflussen (Abbildung 16). [225][226][227][228][229] Diese SAHs scheinen über verschiedene Mechanismen zu wirken, welche noch genauer aufgeklärt werden müssen. [224] Vielfältige SAH-Derivate,wie INP0341, wurden synthetisiert und führten zu einer Verringerung der bakteriellen Pathogenität.…”

Section: Typ-iii-sekretionssysteme (T3ss)unclassified

“…[224] Vielfältige SAH-Derivate,wie INP0341, wurden synthetisiert und führten zu einer Verringerung der bakteriellen Pathogenität. [225][226][227][228][229] Diese SAHs scheinen über verschiedene Mechanismen zu wirken, welche noch genauer aufgeklärt werden müssen. [230] In einem weiteren Ansatz konnte durch ein Screening von Substanzbibliotheken in einem zellulären Reporter-Assay das Phenoxyacetamid MBX 1641 als wirksamer Inhibitor gegen das T3SS in P. aeruginosa (IC 50 % 10 mm)i dentifiziert werden (Abbildung 16).…”

Section: Typ-iii-sekretionssysteme (T3ss)unclassified

Über bisherige Denkweisen hinaus – neue Wirkstoffe zur Überwindung der Antibiotika‐Krise

et al. 2018

View full text Add to dashboard Cite

Die öffentliche Wahrnehmung von Antibiotika als verlässliche Arzneimittel veränderte sich drastisch, als Meldungen über “multiresistente Super‐Erreger” die Nachrichten aufrüttelten. Während die Ursachen für die bakterielle Resistenzentwicklung schnell erkannt wurden, befindet sich die Forschung zur Wiedergewinnung von Antibiotika als effektive Arzneistoffe immer noch am Anfang. Dieser Aufsatz umfasst zahlreiche Aspekte des Entwicklungsprozesses neuer Antibiotika, von der Grundlagenforschung bis zum fertigen Medikament. Er bietet einen interdisziplinären Überblick über Methoden zur Identifizierung neuer Antibiotika und erörtert Strategien, um ihren molekularen Wirkmechanismus aufzuklären. Die Darstellung ausgewählter Antibiotika, die kürzlich mithilfe dieser Plattformen entdeckt wurden, verdeutlicht die Effizienz der Ansätze und hebt vielversprechende klinische Kandidaten mit therapeutischem Potential hervor. Zusätzlich wird das Konzept von Molekülen erörtert, die Krankheitserreger “entwaffnen”, indem sie Schlüsselpunkte der Virulenz adressieren. Der Aufsatz schließt mit einer kritischen Beurteilung jener antibakteriellen Wirkstoffe, die sich derzeit in klinischer Entwicklung befinden. Insgesamt soll dieser Aufsatz ausgewählte, innovative antibakterielle Ansätze verknüpfen, um interdisziplinäre Partnerschaften zwischen Chemikern aus der akademischen und industriellen Forschung anzuregen.

show abstract

“…Recently, urea derivatives obtained from sulfamethoxazole (SMX) 1 have been proposed as potential inhibitors of human carbonic anhydrases [ 11 ], anticancer [ 12 , 13 ], and antimicrobial agents [ 14 , 15 ]. Importantly, we reported the synthesis and antimicrobial activity of nine sulfamethoxazole-based ureas and corresponding cyclic analogues, imidazolidine-2,4,5-triones.…”

Section: Introductionmentioning

confidence: 99%

Novel Sulfamethoxazole Ureas and Oxalamide as Potential Antimycobacterial Agents

2017

View full text Add to dashboard Cite

Infections caused by Mycobacterium tuberculosis (Mtb.) and nontuberculous mycobacteria (NTM) are considered to be a global health problem; current therapeutic options are limited. Sulfonamides have exhibited a wide range of biological activities including those against mycobacteria. Based on the activity of 4-(3-heptylureido)-N-(5-methylisoxazol-3-yl)benzenesulfonamide against NTM, we designed a series of homologous sulfamethoxazole-based n-alkyl ureas (C1–C12), as well as several related ureas and an oxalamide. Fifteen ureas and one oxalamide were synthesized by five synthetic procedures and characterized. They were screened for their activity against Mtb. and three NTM strains (M. avium, M. kansasii). All of them share antimycobacterial properties with minimum inhibitory concentration (MIC) values starting from 2 µM. The highest activity showed 4,4′-[carbonylbis(azanediyl)]bis[N-(5-methylisoxazol-3-yl)benzenesulfonamide] with MIC of 2–62.5 µM (i.e., 1.07–33.28 µg/mL). Among n-alkyl ureas, methyl group is optimal for the inhibition of both Mtb. and NTM. Generally, longer alkyls led to increased MIC values, heptyl being an exception for NTM. Some of the novel derivatives are superior to parent sulfamethoxazole. Several urea and oxalamide derivatives are promising antimycobacterial agents with low micromolar MIC values.

show abstract

Design, synthesis and evaluation of novel polypharmacological antichlamydial agents

Cited by 15 publications

References 25 publications

Thinking Outside the Box—Novel Antibacterials To Tackle the Resistance Crisis

Thinking Outside the Box—Novel Antibacterials To Tackle the Resistance Crisis

Über bisherige Denkweisen hinaus – neue Wirkstoffe zur Überwindung der Antibiotika‐Krise

Novel Sulfamethoxazole Ureas and Oxalamide as Potential Antimycobacterial Agents

Contact Info

Product

Resources

About