Synthesis and evaluation of functionalized benzoboroxoles as potential anti-tuberculosis agents

Alam, Mohammad A.; Arora, Kriti; Gurrapu, Shirisha; Jonnalagadda, Sravan K.; Nelson, Grady L.; Kiprof, Paul; Jonnalagadda, Subash C.; Mereddy, Venkatram R.

doi:10.1016/j.tet.2016.03.038

Cited by 24 publications

(10 citation statements)

References 53 publications

(12 reference statements)

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“…132,133 In addition, benzoboroxoles also show inhibitory activity against several enzymes such as carbonic anhydrases and they are potential anti-tuberculosis agents. 134,135 However, this class of compound has recently drawn particular interest from their potential application as carbohydrate receptors, as they can bind sugars under physiological conditions. 136 Compared to their boronic acid counterparts, benzoboroxoles are able to bind sugars in the pyranose form, at pH values that are more suitable for biological systems.…”

Section: Benzoboroxolesmentioning

confidence: 99%

The challenges of glycan recognition with natural and artificial receptors

et al. 2019

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Section: Benzoboroxolesmentioning

confidence: 99%

The challenges of glycan recognition with natural and artificial receptors

et al. 2019

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“…Zhang et al described a set of interesting, highly active chalcone-benzoxaborole hybrids [14], but further studies are needed to reveal to what extent the observed activity resulted from the introduction of the boron-containing moiety. Suman et al synthesized a series of 6-aminobenzoxaborole derivatives, of which some showed high antiproliferative activity in pancreatic cancer cells (MIA-PaCa-2) [17], whereas some other examples of 6-aminobenzoxaborole-derived compounds showed no activity in MCF7 at a concentration of 50 μM [40], similarly to a set of β-ketobenzoxaboroles synthesized by Sravan Kumar et al [18]. In both cases, the described compounds had a much more complex chemical structure than the derivatives reported herein.…”

Section: Discussionmentioning

confidence: 99%

Discovering simple phenylboronic acid and benzoxaborole derivatives for experimental oncology – phase cycle-specific inducers of apoptosis in A2780 ovarian cancer cells

et al. 2018

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Objective The aim of the study was to evaluate the antiproliferative potential of simple phenylboronic acid and benzoxaborole derivatives as well as to provide preliminary insight into their mode of action in cancer cells in vitro. Methods The antiproliferative activity was assessed in five diverse cancer cell lines via the SRB method (sulforhodamine B) or MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method after 72 h of treatment. Further studies of the mechanism of action consisted of the influence of the compounds on cell cycle progression and apoptosis induction, which was assessed by flow cytometry, caspase-3 enzymatic activity, fluorescence microscopy and western blot analysis. Results A clear structure-activity relationship was observed for both groups of compounds with several representatives evaluated as highly active antiproliferative agents with low micromolar [Formula: see text] values. 2-Fluoro-6-formylphenylboronic acid (18) and 3-morpholino-5-fluorobenzoxaborole (27) exhibited strong cell cycle arrest induction in G/M associated with caspase-3 activation in an A2780 ovarian cancer cell line. These events were accompanied by a mitotic catastrophe cell morphology and an increased percentage of aneuploid and tetraploid cells. Further experiments indicated that the compounds were phase cycle-specific agents since cells co-treated with hydroxyurea were less sensitive. The observed cell cycle arrest resulted from significant p21 accumulation and was associated neither with cyclin B1 nor β-tubulin degradation. Conclusion Phenylboronic acid and benzoxaborole derivatives were found to be highly promising antiproliferative and proapoptotic compounds with a cell cycle-specific mode of action. The presented data support their candidacy for further studies as a novel class of potential anticancer agents.

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“…The BCG-vaccine Danish Strain 1331 (BCG-vaccine) from Chile (Statens Serum Institute, Denmark) and the NIH BCG-brain and BCG-lung clinical isolates were confirmed as M. tuberculosis complex by Maldi-TOF-MS and antibiotic susceptibility was performed. Antibiotic susceptibility testing of clinical and vaccine strains was performed as described previously ( table 2 ) [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

Tissue specific diversification, virulence and immune response to Mycobacterium bovis BCG in a patient with an IFN-γ R1 deficiency

et al. 2020

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We characterized Mycobacterium bovis BCG isolates found in lung and brain samples from a previously vaccinated patient with IFNγR1 deficiency. The isolates collected displayed distinct genomic and phenotypic features consistent with host adaptation and associated changes in antibiotic susceptibility and virulence traits. Background: We report a case of a patient with partial recessive IFNγR1 deficiency who developed disseminated BCG infection after neonatal vaccination (BCG-vaccine). Distinct M. bovis BCGvaccine derived clinical strains were recovered from the patient's lungs and brain. Methods: BCG strains were phenotypically (growth, antibiotic susceptibility, lipid) and genetically (whole genome sequencing) characterized. Mycobacteria cell infection models were used to assess apoptosis, necrosis, cytokine release, autophagy, and JAK-STAT signaling. Results: Clinical isolates BCG-brain and BCG-lung showed distinct Rv0667 rpoB mutations conferring high-and low-level rifampin resistance; the latter displayed clofazimine resistance through Rv0678 gene (MarR-like transcriptional regulator) mutations. BCG-brain and BCG-lung showed mutations in fadA2, fadE5, and mymA operon genes, respectively. Lipid profiles revealed reduced levels of PDIM in BCG-brain and BCG-lung and increased TAGs and Mycolic acid components in BCG-lung, compared to parent BCG-vaccine. In vitro infected cells showed that the BCG-lung induced a higher cytokine release, necrosis, and cell-associated bacterial load effect when compared to BCG-brain; conversely, both strains inhibited apoptosis and altered JAK-STAT signaling. Conclusions: During a chronic-disseminated BCG infection, BCG strains can evolve independently at different sites likely due to particular microenvironment features leading to differential antibiotic resistance, virulence traits resulting in dissimilar responses in different host tissues.

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Synthesis and evaluation of functionalized benzoboroxoles as potential anti-tuberculosis agents

Cited by 24 publications

References 53 publications

The challenges of glycan recognition with natural and artificial receptors

The challenges of glycan recognition with natural and artificial receptors

Discovering simple phenylboronic acid and benzoxaborole derivatives for experimental oncology – phase cycle-specific inducers of apoptosis in A2780 ovarian cancer cells

Tissue specific diversification, virulence and immune response to Mycobacterium bovis BCG in a patient with an IFN-γ R1 deficiency

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