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

Abstract

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.

Elemental mapping of half-sandwich azopyridine osmium arene complexes in cancer cells

“…S2-4 †) also exhibited clear cell outlines with rounded shapes (mean roundness factor, RF: 0.77 ± 0.14; where RF = 1 implies perfect circularity), large cell nuclei, and overall area ranged between 215-439 µm 2 (mean area = 303 ± 93 µm 2 ). All of this correlated well with the rounded morphologies and nuclei, [28][29][30] and typical size (<20 µm in diameter; expected area around 314 µm 2 ) 31 reported for this cell line. Moreover, observation of the nuclei of the control cells mapped (shown by the concentrated regions of Zn), 32 suggested that the wide variation between their areas (ESI, Table S1 †) could be explained by their different stages of the cell cycle.…”

Design, Synthesis, and Structure–Activity Relationship of 7-Propanamide Benzoxaboroles as Potent Anticancer Agents

“…This work is the first to show that benzoxaboroles may serve as potent and efficacious anticancer agents. Although there are existing reports commenting on their anticancer activity, the reported potency at cellular level was not ideal and in vivo efficacy was not reported . However, the intracellular target of our benzxoaboroles remains to be elucidated.…”

“…Although there are existing reports commenting on their anticancer activity, the reported potency at cellular level was not ideal and in vivo efficacy was not reported. 30 However, the intracellular target of our benzxoaboroles remains to be elucidated. They were demonstrated to effectively induce cancer cell apoptosis through the caspase 3/9 and PARP pathways and inhibited colony formation.…”

Merging Electron Deficient Boronic Centers with Electron-Withdrawing Fluorine Substituents Results in Unique Properties of Fluorinated Phenylboronic Compounds

“…Recently, it was found that 2-fluoro-6-formylphenylboronic acid and 3-morpholino-5-fluorobenzoxaborole exhibit strong cell cycle arrest induction in G2/M associated with caspase-3 activation in an A2780 ovarian cancer cell line [ 87 ].…”