Discovery and Syntheses of “Superbug Challengers”—Platensimycin and Platencin

Palanichamy, Kalanidhi; Kaliappan, Krishna P.

doi:10.1002/asia.200900423

Cited by 59 publications

(24 citation statements)

References 251 publications

(188 reference statements)

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“…A handful of analogs housing either a modified aromatic or tetracyclic domain have been produced. Not one of the compounds created has improved activity or more desirable bioavailability, emphasizing the importance of each functional group of platensimycin [15,16]. This roadblock is consistently encountered in attempts to improve any of the reported FASII-targeted natural products (cerulenin, thiolactomycin, and platensin) [15,17,18].…”

Section: Natural Product Inhibitors Of Fasiimentioning

confidence: 99%

Is bacterial fatty acid synthesis a valid target for antibacterial drug discovery?

Parsons

Rock

2011

Current Opinion in Microbiology

142

119

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The emergence of resistance against most current drugs emphasizes the need to develop new approaches to control bacterial pathogens, particularly Staphylococcus aureus. Bacterial fatty acid synthesis is one such target that is being actively pursued by several research groups to develop anti-Staphylococcal agents. Recently, the wisdom of this approach has been challenged based on the ability of a Gram-positive bacterium to incorporate extracellular fatty acids and thus circumvent the inhibition of de novo fatty acid synthesis. The generality of this conclusion has been challenged, and there is enough diversity in the enzymes and regulation of fatty acid synthesis in bacteria to conclude that there isn’t a single organism that can be considered typical and representative of bacteria as a whole. We are left without a clear resolution to this ongoing debate and await new basic research to define the pathways for fatty acid uptake and that determine the biochemical and genetic mechanisms for the regulation of fatty acid synthesis in Gram-positive bacteria. These crucial experiments will determine whether diversity in the control of this important pathway accounts for the apparently different responses of Gram-positive bacteria to the inhibition of de novo fatty acid synthesis in presence of extracellular fatty acid supplements.

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Section: Natural Product Inhibitors Of Fasiimentioning

confidence: 99%

Is bacterial fatty acid synthesis a valid target for antibacterial drug discovery?

Parsons

Rock

2011

Current Opinion in Microbiology

142

119

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“…Platensimycin blocks enzymes involved in the condensation steps in fatty acid biosynthesis. It works by inhibiting beta-ketoacyl synthases I/II (FabF/B) which are key enzymes in the production of fatty acids required for bacterial cell membranes (71).…”

Section: Platensimycinmentioning

confidence: 99%

Antibacterial Agents from Actinomycetes - A Review

Mahajan¹

2012

Front Biosci

104

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“…The advantage of these antibiotics is that they inhibit the bacterial fatty acid biosynthesis, which is essential for the survival of bacteria. Their structures are related with slightly different mechanisms of action, and they target different enzymes in the bacterial fatty acid biosynthesis 123,155…”

Section: Platensimycin and Platencinmentioning

confidence: 99%

“…Modifying either the aromatic portion or the ketolide domain of platensimycin and platencin has produced many analogs recently 158–164. However, none of them have better activity than platensimycin and platencin 155. Thus, to improve their poor pharmacokinetic properties, several congeners of these products have been discovered from the fermentation of broth but, again, none of them have exhibited better activity 165–168.…”

Section: Platensimycin and Platencinmentioning

confidence: 99%

The use of platensimycin and platencin to fight antibiotic resistance

Allahverdiyev¹,

Bağırova²,

Abamor³

et al. 2013

IDR

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Infectious diseases are known as one of the most life-threatening disabilities worldwide. Approximately 13 million deaths related to infectious diseases are reported each year. The only way to combat infectious diseases is by chemotherapy using antimicrobial agents and antibiotics. However, due to uncontrolled and unnecessary use of antibiotics in particular, surviving bacteria have evolved resistance against several antibiotics. Emergence of multidrug resistance in bacteria over the past several decades has resulted in one of the most important clinical health problems in modern medicine. For instance, approximately 440,000 new cases of multidrug-resistant tuberculosis are reported every year leading to the deaths of 150,000 people worldwide. Management of multidrug resistance requires understanding its molecular basis and the evolution and dissemination of resistance; development of new antibiotic compounds in place of traditional antibiotics; and innovative strategies for extending the life of antibiotic molecules. Researchers have begun to develop new antimicrobials for overcoming this important problem. Recently, platensimycin – isolated from extracts of Streptomyces platensis – and its analog platencin have been defined as promising agents for fighting multidrug resistance. In vitro and in vivo studies have shown that these new antimicrobials have great potential to inhibit methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae by targeting type II fatty acid synthesis in bacteria. Showing strong efficacy without any observed in vivo toxicity increases the significance of these antimicrobial agents for their use in humans. However, at the present time, clinical trials are insufficient and require more research. The strong antibacterial efficacies of platensimycin and platencin may be established in clinical trials and their use in humans for coping with multidrug resistance may be allowed in the foreseeable future.

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Discovery and Syntheses of “Superbug Challengers”—Platensimycin and Platencin

Cited by 59 publications

References 251 publications

Is bacterial fatty acid synthesis a valid target for antibacterial drug discovery?

Is bacterial fatty acid synthesis a valid target for antibacterial drug discovery?

Antibacterial Agents from Actinomycetes - A Review

The use of platensimycin and platencin to fight antibiotic resistance

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