Back to Journals » Therapeutics and Clinical Risk Management » Volume 3 » Issue 4

Drug forecast – the peptide deformylase inhibitors as antibacterial agents

Authors David R P Guay

Published 15 September 2007 Volume 2007:3(4) Pages 513—525

David R P Guay

College of Pharmacy, University of Minnesota and Division of Geriatrics, HealthPartners Inc., Minneapolis, MN, USA

Abstract: The relatively rapid development of microbial resistance after the entry of every new antimicrobial into the marketplace necessitates a constant supply of new agents to maintain effective pharmacotherapy. Despite extensive efforts to identify novel lead compounds from molecular targets, only the peptide deformylase inhibitors (PDIs) have shown any real promise, with some advancing to phase I human trials. Bacterial peptide deformylase, which catalyzes the removal of the N-formyl group from N-terminal methionine following translation, is essential for bacterial protein synthesis, growth, and survival. The majority of PDIs are pseudopeptide hydroxamic acids and two of these (IV BB-83698 and oral NVP LBM-415) entered phase I human trials. However, agents to the present have suffered from major potential liabilities. Their in vitro activity has been limited to gram-positive aerobes and some anaerobes and has been quite modest against the majority of such species (MIC90 values ranging from 1–8 mg/L). They have exerted bacteriostatic, not bacteriocidal, activity, thus reducing their potential usefulness in the management of serious infections in the immunocompromised. The relative ease with which microorganisms have been able to develop resistance and the multiple available mechanisms of resistance (mutations in fmt, defB, folD genes; AcrAB/TolC efflux pump; overexpression of peptide deformylase) are worrisome. These could portend a short timespan of efficacy after marketing. Despite these current liabilities, further pursuit of more potent and broader spectrum PDIs which are less susceptible to bacterial mechanisms of resistance is still warranted.

Keywords: peptide deformylase, peptide deformylase inhibitors, actinonin, LBM-415, BB-83698, BB-3497

Download Article [PDF] 

Readers of this article also read:

Silica nanoparticles increase human adipose tissue-derived stem cell proliferation through ERK1/2 activation

Kim KJ, Joe YA, Kim MK, Lee SJ, Ryu YH, Cho DW, Rhie JW

International Journal of Nanomedicine 2015, 10:2261-2272

Published Date: 24 March 2015

Limitations of real-world treatment with atorvastatin monotherapy for lowering LDL-C in high-risk cardiovascular patients in the US

Marrett E, Zhao C, Zhang NJ, Zhang Q, Ramey DR, Tomassini JE, Tershakovec AM, Neff DR

Vascular Health and Risk Management 2014, 10:237-246

Published Date: 25 April 2014

Short-term training of upper gastrointestinal endoscopy for resident doctors in Sotogahama Central Hospital in Aomori, Japan

Soma T, Sakamoto Y, Matsuoka Y, Nakano T, Kamiuttanai M, Akiyama M

Advances in Medical Education and Practice 2013, 4:127-131

Published Date: 9 July 2013

Erratum

Sørensen HT, Friborg S, Rungby J, Christiansen JS, Vaag A, Beck-Nielsen H

Clinical Epidemiology 2012, 4:49-50

Published Date: 20 December 2012

Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties

Gradauer K, Vonach C, Leitinger G, Kolb D, Fröhlich E, Roblegg E, Bernkop-Schnürch A, Prassl R

International Journal of Nanomedicine 2012, 7:2523-2534

Published Date: 21 May 2012

Corrigendum

Schneider EW, Johnson MW

Clinical Ophthalmology 2011, 5:1315-1316

Published Date: 16 September 2011

Magnetic nanoparticles for gene and drug delivery

Stuart C McBain, Humphrey HP Yiu, Jon Dobson

International Journal of Nanomedicine 2008, 3:169-180

Published Date: 6 June 2008

Aging and cosmetic enhancement

Roberta Honigman, David J Castle

Clinical Interventions in Aging 2006, 1:115-119

Published Date: 15 June 2006