Diphenylboron chelate of an 3-hydroxy-N-(2-hydroxyalkyl)hydroxamic acid

2002 ◽  
Vol 58 (11) ◽  
pp. o1215-o1217
Author(s):  
Wolfgang Kliegel ◽  
Ute Schumacher ◽  
Brian O. Patrick ◽  
Steven J. Rettig ◽  
James Trotter
Keyword(s):  
Hydroxamic Acid ◽  
Diphenylboron Chelate

Synthesis and Investigation of Therapeutic Potential of Isoform-Specific HDAC8 Inhibitors for the Treatment of Cutaneous T Cell Lymphoma

2019 ◽  
Vol 19 (7) ◽  
pp. 916-934 ◽  
Author(s):  
Appavoo Umamaheswari ◽  
Ayarivan Puratchikody ◽  
Natarajan Hari
Keyword(s):  
Side Effects ◽  
Inhibitory Activity ◽  
Hydroxamic Acid ◽  
Histone Deacetylase Inhibitors ◽  
Therapeutic Potential ◽  
In Vitro Assays ◽  
Normal Cells ◽  
Standard Drug ◽  
In Silico Studies ◽  
Hdac8 Inhibitors

Background:The available treatment option for any type of cancer including CTCL is chemotherapy and radiation therapy which indiscriminately persuade on the normal cells. One way out for selective destruction of CTCL cells without damaging normal cells is the use of histone deacetylase inhibitors (HDACi). Despite promising results in the treatment of CTCL, these HDACi have shown a broadband inhibition profile, moderately selective for one HDAC class but not for a particular isotype. The prevalence of drug-induced side effects leaves open a narrow window of speculation that the decreased therapeutic efficacy and observed side effects may be most likely due to non specific HDAC isoform inhibition. The aim of this paper is to synthesis and evaluates HDAC8 isoform specific inhibitors.Methods:Based on the preliminary report on the design and in silico studies of 52 hydroxamic acid derivatives bearing multi-substituent heteroaromatic rings with chiral amine linker, five compounds were shortlisted and synthesized by microwave assisted approach and high yielding synthetic protocol. A series of in vitro assays in addition to HDAC8 inhibitory activity was used to evaluate the synthesised compounds.Results:Inhibitors 1e, 2e, 3e, 4e and 5e exerted the anti-proliferative activities against CTCL cell lines at 20- 100 µM concentrations. Both the pyrimidine- and pyridine-based probes exhibited μM inhibitory activity against HDAC8. The pyrimidine-based probe 1e displayed remarkable HDAC8 selectivity superior to that of the standard drug, SAHA with an IC50 at 0.1µM.Conclusion:Our study demonstrated that simple modifications at different portions of pharmacophore in the hydroxamic acid analogues are effective for improving both HDAC8 inhibitory activity and isoform selectivity. Potent and highly isoform-selective HDAC8 inhibitors were identified. These findings would be expedient for further development of HDAC8-selective inhibitors.

scholarly journals Suberoylanilide hydroxamic acid enhances the radiosensitivity of lung cancer cells through acetylated wild-type and mutant p53-dependent modulation of mitochondrial apoptosis

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098154
Author(s):  
Kan Wu ◽  
Xueqin Chen ◽  
Xufeng Chen ◽  
Shirong Zhang ◽  
Yasi Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Hydroxamic Acid ◽  
Site Directed Mutagenesis ◽  
Lung Cancer Cells ◽  
Mutant P53 ◽  
Suberoylanilide Hydroxamic Acid ◽  
Mitochondrial Apoptosis ◽  
Wild Type ◽  
Clonogenic Cell

Objective Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, has shown potential as a candidate radiosensitizer for many types of cancers. This study aimed to explore the radiosensitization mechanism of SAHA in lung cancer cells. Methods Mutations in p53 were generated by site-directed mutagenesis using polymerase chain reaction. Transfection was performed to generate H1299 cells carrying wild-type or mutant p53. The radiosensitizing enhancement ratio was determined by clonogenic assays. Mitochondrial apoptosis was detected using JC-1 staining and flow cytometry analysis. Results Our results showed that SAHA induced radiosensitization in H1299 cells expressing wild-type p53, p53R175H or p53P223L, but this enhanced clonogenic cell death was not observed in parental H1299 (p53-null) cells or H1299 cells expressing p53 with K120R, A161T and V274R mutations. In SAHA-sensitized cells, mitochondrial apoptosis was induced following exposure to irradiation. Additionally, we observed that a secondary mutation at K120 (K120R) could eliminate p53-mediated radiosensitization and mitochondrial apoptosis. Conclusions The results of this study suggest that wild-type and specific mutant forms of p53 mediate SAHA-induced radiosensitization by regulating mitochondrial apoptosis, and the stabilization of K120 acetylation by SAHA is the molecular basis contributing to radiosensitization in lung cancer cells.

scholarly journals Study on Chromaticity Removal from Mineral Processing Wastewater with Salicylic Hydroxamic Acid by Granular Activated Carbon Catalyzed Ozonation

Minerals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 359
Author(s):  
Liping Zhang ◽  
Shengnian Wu ◽  
Nan Zhang ◽  
Ruihan Yao ◽  
Eryong Wu
Keyword(s):  
Activated Carbon ◽  
Reaction Time ◽  
Hydroxamic Acid ◽  
Ph Value ◽  
Oxygen Demand ◽  
Granular Activated Carbon ◽  
Mineral Processing ◽  
Ultraviolet Absorption Spectrum ◽  
Experimental Conditions ◽  
Removal Ratio

Salicylic hydroxamic acid is a novel flotation reagent used in mineral processing. However, it impacts the flotation wastewater leaving behind high chromaticity which limits its reuse and affects discharge for mining enterprises. This study researched ozonation catalyzed by the granular activated carbon (GAC) method to treat the chromaticity of the simulated mineral processing wastewater with salicylic hydroxamic acid. The effects of pH value, ozone (O3) concentration, GAC dosage, and reaction time on chromaticity and chemical oxygen demand (CODCr) removal were discussed. The results of individual ozonation experiments showed that the chromaticity removal ratio reached 79% and the effluent chromaticity exceeded the requirement of reuse and discharge when the optimal experimental conditions were pH value 3, ozone concentration 6 mg/L, and reaction time 40 min. The orthogonal experimental results of catalytic ozonation with GAC on chromaticity removal explained that the chromaticity removal ratio could reach 96.36% and the chromaticity of effluent was only 20 when the optimal level of experimental parameters was pH value 2.87, O3 concentration 6 mg/L, GAC dosage 0.06 g/L, reaction time 60 min respectively. The degradation pathway of salicylic hydroxamic acid by ozonation was also considered based on an analysis with ultraviolet absorption spectrum and high-performance liquid chromatography (HPLC).

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