Current data regarding the structure-toxicity relationship of boron-containing compounds

Farfán‐García, Eunice D.; Castillo-Mendieta, N.T.; Ciprés-Flores, F.J.; Padilla‐Martínez, Itzia I.; Trujillo‐Ferrara, José G.; Soriano-Ursúa, Marvin A.

doi:10.1016/j.toxlet.2016.06.018

Cited by 65 publications

(48 citation statements)

References 137 publications

(169 reference statements)

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“…[28] These boron prodrugs release quinone methides and boron acids that are known to have potential toxicity issues. [29][30] There has been a recent approval of a boron-based drug by the FDA 31 showing ROS-prodrugs can be a viable approach. Thus, we seek alternative designs of oxidation activated compounds.…”

Section: Full Papersmentioning

confidence: 99%

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Oxidative Cyclization‐Induced Activation of a Phosphoinositide 3‐Kinase Inhibitor for Enhanced Selectivity of Cancer Chemotherapeutics

et al. 2019

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In this work, we designed a prodrug that reacts with cellular oxidative equivalents leading to ether cleavage and cyclization to release an active phosphatidylinositol 3-kinase (PI3K) inhibitor. We show that the compound reduces affinity for PI3KA relative to the PI3K inhibitor, is slow to intercellularly oxidize, and is resistant to liver microsomes. We observed modest activity in untreated acute myeloid leukemia cells and 14-fold selectivity relative to non-cancerous cells. The cellular activity of the compound can be modulated by the addition of antiox-idants or oxidants, indicating the compound activity is sensitive to cellular reactive oxygen species (ROS) state. Co-treatment with cytosine arabinoside or doxorubicin was used to activate the compound inside cells. We observed strong synergistic activity specifically in acute myeloid leukemia (AML) cancer cells with an increase in selective anticancer activity of up to 90-fold. Thus, these new self-cyclizing compounds can be used to increase the selectivity of anticancer agents.

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Section: Full Papersmentioning

confidence: 99%

“…This design prevents activation in healthy cells that have ROS and likely confers stability to the liver environment. [29][30] There has been a recent approval of a boron-based drug by the FDA 31 showing ROS-prodrugs can be a viable approach. So we propose to make compounds that are activated by large changes in oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Oxidative Cyclization‐Induced Activation of a Phosphoinositide 3‐Kinase Inhibitor for Enhanced Selectivity of Cancer Chemotherapeutics

et al. 2019

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“…Against this background, the numbers of articles in scientific journals on biological effects of boron have increased steadily since 1990 (Farfán-García et al 2016), and important contributions were published in this journal. Important clusters of contemporary research can be among bacteria and specifically among legumes and rhizobia leading to nitrogen-fixing symbiosis.…”

Section: Role Of Boron Compounds In Plantsmentioning

confidence: 99%

“…In fact, since the year 2000, the numbers of studies on the medicinal use of boron-containing compounds have by far exceeded the numbers of reports on boron-related toxicity (Farfán-García et al 2016). For instance, boron-containing structures may influence inotropic and metabotropic receptors, enzyme-linked receptors, and cytoplasmic and nuclear receptors (Soriano-Ursúa et al 2014).…”

Section: Therapeutic Developmentsmentioning

confidence: 99%

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Boron and its compounds: current biological research activities

et al. 2017

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Halogenated boroxine increases propensity to apoptosis in leukemia (UT‐7) but not non‐tumor cells in vitro

et al. 2022

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A hallmark of the development of solid and hematological malignancies is the dysregulation of apoptosis, which leads to an imbalance between cell proliferation, cell survival and death. Halogenated boroxine [K2(B3O3F4OH)] (HB) is a derivative of cyclic anhydride of boronic acid, with reproducible anti‐tumor and anti‐proliferative effects in different cell models. Notably, these changes are observed to be more profound in tumor cells than in normal cells. Here, we investigated the underlying mechanisms through an extensive evaluation of (a) deregulated target genes and (b) their interactions and links with main apoptotic pathway genes upon treatment with an optimized concentration of HB. To provide deeper insights into the mechanism of action of HB, we performed identification, visualization, and pathway association of differentially expressed genes (DEGs) involved in regulation of apoptosis among tumor and non‐tumor cells upon HB treatment. We report that HB at a concentration of 0.2 mg·mL−1 drives tumor cells to apoptosis, whereas non‐tumor cells are not affected. Comparison of DEG profiles, gene interactions and pathway associations suggests that the HB effect and tumor‐‘selectivity’ can be explained by Bax/Bak‐independent mitochondrial depolarization by ROS generation and TRAIL‐like activation, followed by permanent inhibition of NFκB signaling pathway specifically in tumor cells.

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Current data regarding the structure-toxicity relationship of boron-containing compounds

Cited by 65 publications

References 137 publications

Oxidative Cyclization‐Induced Activation of a Phosphoinositide 3‐Kinase Inhibitor for Enhanced Selectivity of Cancer Chemotherapeutics

Oxidative Cyclization‐Induced Activation of a Phosphoinositide 3‐Kinase Inhibitor for Enhanced Selectivity of Cancer Chemotherapeutics

Boron and its compounds: current biological research activities

Halogenated boroxine increases propensity to apoptosis in leukemia (UT‐7) but not non‐tumor cells in vitro

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