Something old, something new: revisiting natural products in antibiotic drug discovery

Wright, Gerard D.

doi:10.1139/cjm-2014-0063

Cited by 245 publications

(229 citation statements)

References 63 publications

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“…The history of antibiotic development suggests that such methods are unlikely to be fruitful against bacteria, which have mechanisms to sense and avoid small molecules including efflux pumps and complex membrane structures such as those of Gram-negative bacteria. 16 Furthermore, they are unlikely to have the structural complexity required to specifically bind a bacterial protease and not its mammalian homolog. In contrast to synthetic drug-like molecules, natural products are highly complex chiral molecules that have been sculpted by millions of years of evolution to enter bacterial cells.…”

Section: Proteases As Drug Targetsmentioning

confidence: 99%

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Bacterial proteases, untapped antimicrobial drug targets

2016

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Bacterial proteases are an extensive collection of enzymes that have vital roles in cell viability, stress response and pathogenicity. Although their perturbation clearly offers the potential for antimicrobial drug development, both as traditional antibiotics and anti-virulence drugs, they are not yet the target of any clinically used therapeutics. Here we describe the potential for and recent progress in the development of compounds targeting bacterial proteases with a focus on AAA+ family proteolytic complexes and signal peptidases (SPs). Caseinolytic protease (ClpP) belongs to the AAA+ family of proteases, a group of multimeric barrel-shaped complexes whose activity is tightly regulated by associated AAA+ ATPases. The opportunity for chemical perturbation of these complexes is demonstrated by compounds targeting ClpP for inhibition, activation or perturbation of its associated ATPase. Meanwhile, SPs are also a proven antibiotic target. Responsible for the cleavage of targeting peptides during protein secretion, both type I and type II SPs have been successfully targeted by chemical inhibitors. As the threat of pan-antibiotic resistance continues to grow, these and other bacterial proteases offer an arsenal of novel antibiotic targets ripe for development.

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Section: Proteases As Drug Targetsmentioning

confidence: 99%

“…In contrast to synthetic drug-like molecules, natural products are highly complex chiral molecules that have been sculpted by millions of years of evolution to enter bacterial cells. 16 These may be the critical leads required to propel bacterial proteases into the realm of bona fide antimicrobial drug targets.…”

Section: Proteases As Drug Targetsmentioning

confidence: 99%

Bacterial proteases, untapped antimicrobial drug targets

2016

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“…Currently, antimicrobial properties are seriously studied due to an enormous increase in bacterial resistance against the excessive and repeated use of antibiotics [13]. The antibiotic resistance crisis has been attributed to the overuse and misuse of these medications, as well as lack of new drug development by the pharma industry due to reduced economic encouragements and challenging regulatory requirements [14][15][16][17]. There are very few studies available about the antimicrobial activity of nanoCuO.…”

Section: Introductionmentioning

confidence: 99%

CuO NANOPARTICLES: SYNTHESIS, CHARACTERIZATION AND THEIR BACTERICIDAL EFFICACY

2017

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Objective: In the present study copper oxide (CuO) nanoparticles were synthesized and characterized. The antibacterial activity of CuO nanoparticles was carried out against Escherichia coli, Proteus vulgaris, Staphylococcus aureus and Streptococcus mutans. Methods:The synthesis was carried out by coprecipitation method using copper sulfate and sodium hydroxide as precursors. The synthesized copper oxide nanoparticles were characterized by using X-ray diffraction (XRD), Fourier transforms infrared spectroscopy (FT-IR), UV-vis spectroscopy and scanning electron microscope (SEM) with Dept of Physics, acharya Nagarjuna University, NH16, Nagarjuna Nagar, Guntur, Andhra Pradesh 522510 Email: peddikiranmayi@gmail.comEnergy Dispersive X-ray Analysis (EDX) techniques. Besides, this study determines the antibacterial activity and minimum inhibitory concentration (MIC) of CuO nanoparticles against gram-positive (Staphylococcus aureus and Streptococcus mutans) and gram-negative (E. coli and Proteus vulgaris) bacteria. Results:The average crystallite size of CuO nanoparticles was found to be 19 nm by X-ray diffraction. FT-IR spectrum exhibited vibrational modes at 432 cm -1 , 511 cm -1 and 611 cm -1 Keywords: CuO nanoparticles, XRD, FTIR, SEM, EDS, Antibacterial activity were assigned for Cu-O stretching vibration. According to UV-Vis spectrum, two bands were observed at 402 nm and 422 nm. ED's spectrum shows only elemental copper (Cu) and oxide (O) and no other elemental impurity was observed. The antimicrobial assay revealed that Proteus vulgaris showed a maximum zone of inhibition (37 mm) at 50 mg/ml concentration of CuO nanoparticles. Conclusion:In conclusion, copper oxide is a good antibacterial agent against both gram positive and gram-negative organisms.

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“…Antibiotics treat infections in patients having chronic diseases, receiving chemotherapy, or having surgeries such as organ transplants and cardiac surgery [24][25][26]. Moreover, antibiotics help to extend life expectancy by changing outcomes of bacterial infections [27].…”

Section: Antibiotics Versus Bacteriocinsmentioning

confidence: 99%

A Comparative Study of Antimicrobial Profile Having Broad Spectrum Bacteriocins Against Antibiotics

Imran

Gupta

Arora

et al. 2017

Asian J Pharm Clin Res

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Bacteriocins are ribosomally synthesized antimicrobial peptides produced by microbes owned by different eubacterial taxonomic branches. Most of them are small cationic membrane-active compounds that form pores in the targeted cells, disrupting membrane possibilities, and triggering cell fatality. The availability of small cationic peptides with antimicrobial activity is a protection strategy found not only in bacteria but also in plants and animals. The antibiotics which have extensive applications in the treatment of various bacterial diseases have developed alarming resistance against them in many pathogens due to improper use besides this antibiotics have adverse side effects also. There are an extensive variety of bacteriocins made by different bacterial genera have promising alternative to antibiotics that needs to be further studied to show the no existence of undesirable effects, which must be performed both in vitro and in vivo experimental systems. Most of the bacteriocin have narrow spectrum of their activity and effective only on the related species. There is an urgent need for the identification of broad-spectrum bacteriocins isolated from the species from different habitats that can be effective against both Gram-positive and Gram-negative pathogens. In this review, we focus on the main physical and chemical characteristics of broad-spectrum bacteriocin and discuss their application as an alternative option to antibiotics.

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Something old, something new: revisiting natural products in antibiotic drug discovery

Cited by 245 publications

References 63 publications

Bacterial proteases, untapped antimicrobial drug targets

Bacterial proteases, untapped antimicrobial drug targets

CuO NANOPARTICLES: SYNTHESIS, CHARACTERIZATION AND THEIR BACTERICIDAL EFFICACY

A Comparative Study of Antimicrobial Profile Having Broad Spectrum Bacteriocins Against Antibiotics

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