The influence of fluorine position on the properties of fluorobenzoxaboroles

Adamczyk‐Woźniak, Agnieszka; Cabaj, Małgorzata Katarzyna; Dominiak, Paulina M.; Gajowiec, Patrycja; Gierczyk, Błażej; Lipok, Jacek; Popenda, Łukasz; Schroeder, Grzegorz; Tomecka, Ewelina; Urbański, Piotr M.; Wieczorek, Dorota; Sporzyński, Andrzej

doi:10.1016/j.bioorg.2015.05.004

Cited by 28 publications

(29 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to PBA derivatives, the acidity of the compounds appeared to play an important role since p K a lowering from 7.39 and 7.42 for 19 and 23 , respectively, to 6.97 observed for 21 was accompanied by a significant increase in biological activity. However, 20 and 22 showed poor antiproliferative potential despite their even lower p K a (6.36 and 6.57, respectively) [21, 24], indicating the presence of at least several factors affecting the structure-activity relationships. Interestingly, we observed similar dependencies on several fungal strains [24], which might suggest the compounds’ common molecular target (potentially leucyl-tRNA synthetase) in both cases.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2018

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Compounds 1 , 4 and 6–11 are commercially available. The following compounds have been synthesized by procedures described elsewhere: 2 [19], 3 [20], 5 [21], 14 [22], 15–18 [23], 19 [21], 20 [24], 21 [25], 22–23 [24], 24–26 [21]. Compounds 12 , 13 and 27 were synthesized similarly to their analogues 8 , 2 , and 25 , respectively.…”

Section: Methodsmentioning

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…The influence of the fluorine substituent on the Lewis acidity of the boronic esters was also investigated . Recently, the influence of the position of the fluorine atom on the structures, spectral characteristics, and biological activity has been investigated for fluorobenzoxaboroles . Similar results for fluoro‐substituted (formylphenyl)boronic acids have been also published …”

Section: Introductionmentioning

confidence: 96%

Fluorinated Boronic Acids: Acidity and Hydrolytic Stability of Fluorinated Phenylboronic Acids

et al. 2017

Self Cite

View full text Add to dashboard Cite

Abstract:The acidity constants and hydrolytic stability of all isomers of fluoro-substituted phenylboronic acids (F 1 -F 5 ) have been determined by both spectrophotometric and potentiometric methods. The introduction of fluorine into the aromatic ring enhances the Lewis acidity of boronic acids, depending on the position and number of fluorine substituents. Results of both methods show good agreement in most of the cases. To explain the observed discrepancies for several compounds, sta-

show abstract

“…The activity of 3 was however lower than that the one reported for Tavaborole in the literature study that used exactly the same protocol as the one herein. 8,28 Bis(4-uorobenzoxaborole) 2 also showed noteworthy activity against the tested microorganisms. Compound 2 inhibited the fungal growth less than compound 3, and only in case of Fusarium strains the activity was signicantly higher.…”

Section: Microbiological Evaluation Of Piperazine Bis(benzoxaboroles)mentioning

confidence: 85%

“…7 It was shown that the presence of a uorine substituent as well as its position inuences the overall bioactivity, which was showcased comparing the antifungal action of four uorobenzoxaboroles, varying in the position of uorine on the benzene ring. 8 The effect of uorine on the action of drugs is complex and covers, among others, such aspects as its impact on acidity, lipophilicity as well as the inuence on the mechanism of action. 9 It is worth mentioning that in addition to Kerydin®, about 25% of the currently available drugs contain uorine.…”

Section: Introductionmentioning

confidence: 99%