Optimizing the antibacterial activity of a lead structure discovered by ‘SAR by MS’ technology

Jefferson, Elizabeth A.; Seth, Punit P.; Robinson, Dale; Winter, Dana K.; Miyaji, Alycia; Risen, Lisa M.; Osgood, Stephen A.; Bertrand, Myra; Swayze, Eric E.

doi:10.1016/j.bmcl.2004.08.033

Cited by 12 publications

(6 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the assembled compounds inhibited translation in vitro , they had no antibacterial activity (Figure B). In a follow-up work, 17 was further optimized to afford the antibacterial 18 , which had a minimum inhibitory concentration (MIC) of 3–6 μM against Stapholococcus aureus and 6–13 μM against Escherichia coli (Figure B) …”

Section: Introductionmentioning

confidence: 99%

Fragment-Based Approaches to Identify RNA Binders

et al. 2023

View full text Add to dashboard Cite

Although fragment-based drug discovery (FBDD) has been successfully implemented and well-explored for protein targets, its feasibility for RNA targets is emerging. Despite the challenges associated with the selective targeting of RNA, efforts to integrate known methods of RNA binder discovery with fragmentbased approaches have been fruitful, as a few bioactive ligands have been identified. Here, we review various fragment-based approaches implemented for RNA targets and provide insights into experimental design and outcomes to guide future work in the area. Indeed, investigations surrounding the molecular recognition of RNA by fragments address rather important questions such as the limits of molecular weight that confer selective binding and the physicochemical properties favorable for RNA binding and bioactivity.

show abstract

Section: Introductionmentioning

confidence: 99%

Fragment-Based Approaches to Identify RNA Binders

et al. 2023

View full text Add to dashboard Cite

show abstract

“…The furan-based biaryl motif is an intriguing molecular framework which serves as a pivotal core for a range of bioactive molecules. The furan biaryl motif is an integral feature of a number of kinase inhibitors including pan-Pim (1) 1 and class I phosphoinositide 3-kinase 2 inhibitors (2), a family of Bcl-xL inhibitors (3), 3 HIV-1 fusion inhibitors (4), 4 in addition to a class of antibacterial agents (5) 5 (Figure 1). However, of particular interest to our research, the furan-based biaryl motif forms the core of a number of small molecules possessing inhibitory activity within the hedgehog signalling pathway such as 6.…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, a noteworthy feature of the furanyl-biaryl scaffold is that in contrast to the majority of biaryl molecular frameworks, modelling 9 and crystallographic data 10 demonstrate that this system preferentially adopts a planar conformation. 1 and class I phosphoinositide 3kinase (2) 2 inhibitors, along with the Bcl-xL inhibitor (3), 3 the HIV-1 fusion inhibitors (4), 4 the gram-negative antibacterial agent (5), and the hedgehog signalling pathway inhibitor (6). 6,7 Figure 2: Co-crystallised structure of 3-{5-[5-(4-chloro-phenyl)-furan-2ylmethylene]-4-oxo-2-thioxo-thiazolidin-3-yl}-propionic acid with the Bacillus anthracis lethal factor metalloproteinase.…”

Section: Introductionmentioning

confidence: 99%

An efficient continuous flow approach to furnish furan-based biaryls

et al. 2014

View full text Add to dashboard Cite

Suzuki cross-couplings of 5-formyl-2-furanylboronic acid with activated or neutral aryl bromides were performed under continuous flow conditions in the presence of (Bu)4N(+)F(-) and the immobilised t-butyl based palladium catalyst CatCart™ FC1032™. Deactivated aryl bromides and activated aryl chlorides were cross-coupled with 5-formyl-2-furanylboronic in the presence of (Bu)4N(+)OAc(-) using the bis-triphenylphosphine CatCart™ PdCl2(PPh3)2-DVB. Initial evidence indicates the latter method may serve as a universal approach to conduct Suzuki cross-couplings with the protocol successfully employed in the synthesis of the current gold standard Hedgehog pathway inhibitor LDE225.

show abstract

“…Biaryl frameworks are often found in a variety of natural products and pharmacophores, such as vancomycin,1 gossypol,1 shizandrin,1 follicle‐stimulating hormone receptor agonists,2 anti‐HIV agents,3 antihypertensive drugs,4 those with antibacterial activity against Gram‐positive bacteria,5 and so on. While these compounds are widely used for various purposes, arylation of the pyridine frameworks is commonly performed by transition‐metal‐catalyzed coupling reactions using phenylboronic acids (Suzuki reaction) or phenylmagnesium bromide (Kumada–Tamao reaction).…”

Section: Introductionmentioning

confidence: 99%

Niobium‐Based Nickel–Tungsten Hydrotreatment Catalysts with Enhanced Isomerization Properties

et al. 2014

View full text Add to dashboard Cite

Alumina‐supported NiW catalysts doped with Nb were prepared with different W contents and different Ni/W ratios. Studies of the sulfide state by TEM and X‐ray photoelectron spectroscopy (XPS) demonstrated the influence of Nb on the sulfidation of W and Ni. The catalytic performance of the solids was evaluated in toluene hydrogenation and cyclohexane isomerization and was compared to that of Nb‐free catalysts. The presence of Nb resulted in a decrease of the hydrogenation activity at low W content and low Ni/W ratio, in agreement with XPS and TEM characterizations. However, increasing the W content and the Ni/W ratio increased the hydrogenation activity. Regardless of the W and Ni content, cyclohexane conversion was significantly improved by the presence of Nb. The most efficient catalyst of the series, with a W content of 15 wt % WO3 and a Ni/W ratio of 0.9, showed slightly higher activity for hydrogenation than that of a Nb‐free NiW catalyst. Also, the isomerization activity was greatly enhanced, demonstrating the potential of these Nb‐based catalyst formulations.

show abstract

Optimizing the antibacterial activity of a lead structure discovered by ‘SAR by MS’ technology

Cited by 12 publications

References 15 publications

Fragment-Based Approaches to Identify RNA Binders

Fragment-Based Approaches to Identify RNA Binders

An efficient continuous flow approach to furnish furan-based biaryls

Niobium‐Based Nickel–Tungsten Hydrotreatment Catalysts with Enhanced Isomerization Properties

Contact Info

Product

Resources

About