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Plant-Based Adjunct Therapy for Tuberculosis
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Lydia Gibango, Anna-Mari Reid, Jonathan L. Seaman, Namrita Lall
β-lactamase inhibitors are mainly used to overcome the resistance to β-lactam antibiotics. As previously mentioned, these adjuvants protect against the inactivation of the antibiotic by enzymes. Bacterial inactivation involves β-lactamases that hydrolyze the β-lactam core of β-lactams through a process based on acylation-deacylation (González-Bello, 2017). In the 1980s, the first β-lactamase inhibitor was used in combination with penicillin. Diazabicyclooctanes have been under investigation since the mid-1990s as β-lactam mimics, and later were found to be efficient β-lactamase inhibitors (Bush, 2018). Boronic acids are used as transition state analogs. The development of these compounds was discovered when serine proteases were inhibited by boronic acids (Smoum et al., 2012).
Laboratory Detection of β-Lactam Resistance in Enterobacterales
Published in Firza Alexander Gronthoud, Practical Clinical Microbiology and Infectious Diseases, 2020
The inhibitors used are: Boronic acid to inhibit class A KPC.EDTA to inhibit class B metallo-β-lactamase.Cloxacillin to inhibit class C AmpC β-lactamases. This test is used to differentiate between AmpC hyperproduction plus porin loss and carbapenemase-production.
Proteasome and Protease Inhibitors
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
N. E. Franke, J. Vink, J. Cloos, Gertjan J. L. Kaspers
Currently, many proteasome inhibitors have been described, including carbobenzoxy-L-leucyl-L-leucyl-leucinal (MG-132), N-acetyl leucyl-leucyl norlucinal (ALLnL), lactacystin, epoxomycin, bortezomib (PS-341), and salinosporamide A (NPI-0052) (36,39–42). Features of the most well-described proteasome inhibitors are summarized in Table 1. These inhibitors can be classified into five major groups: peptide aldehydes, peptide vinyl sulfones, peptide boronates, peptide epoxyketones, and β-lactones (43). Epoxyketones seem quite specific but have not been studied very well, while peptide aldehydes, peptide vinyl sulfones and β-lactones lack enzyme specificity, are metabolically instable, or bind irreversible to the proteasome (36). Peptide boronic acids seem most suitable for clinical usage. They dissociate in a slower rate from the proteasome, have up to 1,000-fold higher potency than peptide aldehydes, are selective, and bind reversible to the proteasome (36,44,45).
Evaluation of a tiered in vitro testing strategy for assessing the ocular and dermal irritation/corrosion potential of pharmaceutical compounds for worker safety
Published in Cutaneous and Ocular Toxicology, 2018
Jessica C. Graham, Nathan Wilt, Gertrude-Emilia Costin, Caren Villano, Jackie Bader, Lindsay Krawiec, Elizabeth Sly, Janet Gould
When considering the number of compounds correctly predicted plus the number over-predicted [(# correctly predicted) + (# over-predicted)]/total # of test compounds), 87% for BCOP and 100% for the SIT, the performance of the in vitro methods was considered acceptable as part of the testing strategy utilized for PCs to protect employee health and communicate potential hazards. The analysis of chemical structures (Table 3) and the ability or inability of the in vitro studies to correctly predict their dermal and ocular hazards was also considered. Although the relationship between chemical structural group and study result is not fully understood, the most noteworthy results for concordance within our dataset are included here. The in vivo study results for nitro aromatic compounds were aligned with the in vitro eye and skin irritation study results (2/2; PC-12 and PC-13). In the case of halogenated heterocycles (PC-7 through PC-11), in vitro skin irritation predictions were generally concordant with the in vivo studies (5/5 accurately predicted, all free bases). The halogenated heterocycles were also either accurately predicted by the BCOP or slightly over-predicted with 3/5 predicted to be mild irritants in vitro vs. being non-irritating in vivo. Boronic acids were not skin irritants in vitro or in vivo and were under-predicted by the BCOP as non-irritants, but were mild to moderate eye irritants in vivo (2/2, PC-5 and PC-6; Table 1).
Improving cellular uptake of therapeutic entities through interaction with components of cell membrane
Published in Drug Delivery, 2019
Renshuai Zhang, Xiaofei Qin, Fandong Kong, Pengwei Chen, Guojun Pan
Although boronic acid first gained attention as sugar-binding agents, the major development was connected with their biological action (Gupta & Simpson, 2015). The studies involving incorporation of boronic acid into materials for cargoes delivery was very little. However, the safety and effectiveness of boronic acid-decorated nanoparticles have been demonstrated in mice. Jiang et al. reported that PBA-decorated chitosan nanoparticles could penetrate deeper and accumulate more in tumor area than non-decorated ones. Furthermore, PBA-decorated chitosan nanoparticles showed superior efficacy in restricting tumor growth and prolonging the survival time of tumor-bearing mice than free drug and drug-loaded chitosan nanoparticles (Wang et al., 2016). Also, boronic acid-rich protein nanoparticles composed of bovine serum albumin (BSA) and poly(N-3-acrylamidophenylboronic acid) showed dominantly liver-targeting and significant washout resistant ability compared to those boronic acid-absent nanoparticles in vivo study, which was attributed to the interaction between SA residues in the liver and boronic acid groups of the nanoparticles (Wang et al., 2013). Additionally, there was no hepatic and cardiac toxicities in vivo antitumor examination in orthotopic liver cancer model. Deshayes et al. reported that the modification of PBA could maintain micelles’ accumulation level in the tumor even after 48 h injection due to the interaction between PBA and SA groups on the surface of cancer cells, whereas the amount of micelles without PBA decreased obviously (Figure S4) (Deshayes et al., 2013). The extension of retention time increased the anticancer efficiency and showed no side effects.
The current progress in the use of boron as a platform for novel antiviral drug design
Published in Expert Opinion on Drug Discovery, 2022
Shuo Wang, Yujie Ren, Zhao Wang, Xiangyi Jiang, Shujing Xu, Xujie Zhang, Shujie Zhao, Waleed A Zalloum, Xinyong Liu, Peng Zhan
Boronic acids can couple with the ribose units of nucleotides and interact with key nucleophilic residues in the subsite by forming a direct reversible covalent bond [61]. Accordingly, GlaxoSmithKline company inserted boronic acid pharmacophore into compound 10 (Figure 3B) to investigate whether this strategy could bring advantages for targeting a subset of NS5B polymorphs and resistant mutants [62]. Among them, compound 11 (Figure 3B) inhibited HCV replication well in a subgenomic replication system (replicon GT1a, GT1b, GT1a 316Y, and GT1b 316 N) with EC50 values in the range of 1.7–3.2 nM. The boronic acid moiety was found to be a critical pharmacophoric feature for efficacy [62].