scholarly journals Molecular and Therapeutic Potential and Toxicity of Valproic Acid

2010 ◽  
Vol 2010 ◽  
pp. 1-18 ◽  
Author(s):  
Sébastien Chateauvieux ◽  
Franck Morceau ◽  
Mario Dicato ◽  
Marc Diederich
Keyword(s):  
Valproic Acid ◽  
Clinical Trials ◽  
Side Effects ◽  
Histone Deacetylase Inhibitors ◽  
Short Chain Fatty Acid ◽  
Therapeutic Potential ◽  
Mood Stabilizer ◽  
Chain Fatty Acid ◽  
Histone Deacetylation ◽  
Transcription Sites

Valproic acid (VPA), a branched short-chain fatty acid, is widely used as an antiepileptic drug and a mood stabilizer. Antiepileptic properties have been attributed to inhibition of Gamma Amino Butyrate (GABA) transaminobutyrate and of ion channels. VPA was recently classified among the Histone Deacetylase Inhibitors, acting directly at the level of gene transcription by inhibiting histone deacetylation and making transcription sites more accessible. VPA is a widely used drug, particularly for children suffering from epilepsy. Due to the increasing number of clinical trials involving VPA, and interesting results obtained, this molecule will be implicated in an increasing number of therapies. However side effects of VPA are substantially described in the literature whereas they are poorly discussed in articles focusing on its therapeutic use. This paper aims to give an overview of the different clinical-trials involving VPA and its side effects encountered during treatment as well as its molecular properties.

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 Perspectives on the therapeutic potential of short-chain fatty acid receptors

BMB Reports ◽  
2014 ◽  
Vol 47 (3) ◽  
pp. 173-178 ◽  
Author(s):  
Sunhong Kim ◽  
Jeong-Hoon Kim ◽  
Bi Oh Park ◽  
Young Shin Kwak
Keyword(s):  
Fatty Acid ◽  
Short Chain Fatty Acid ◽  
Therapeutic Potential ◽  
Chain Fatty Acid ◽  
Short Chain

scholarly journals Valproic Acid and Its Amidic Derivatives as New Antivirals against Alphaherpesviruses

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1356
Author(s):  
Sabina Andreu ◽  
Inés Ripa ◽  
Raquel Bello-Morales ◽  
José Antonio López-Guerrero
Keyword(s):  
Valproic Acid ◽  
Herpes Simplex ◽  
Neurological Disorders ◽  
Short Chain Fatty Acid ◽  
Chain Fatty Acid ◽  
Nucleoside Analogues ◽  
Broad Host Range ◽  
Herpes Simplex Viruses ◽  
Neurotropic Viruses ◽  
Global Population

Herpes simplex viruses (HSVs) are neurotropic viruses with broad host range whose infections cause considerable health problems in both animals and humans. In fact, 67% of the global population under the age of 50 are infected with HSV-1 and 13% have clinically recurrent HSV-2 infections. The most prescribed antiherpetics are nucleoside analogues such as acyclovir, but the emergence of mutants resistant to these drugs and the lack of available vaccines against human HSVs has led to an imminent need for new antivirals. Valproic acid (VPA) is a branched short-chain fatty acid clinically used as a broad-spectrum antiepileptic drug in the treatment of neurological disorders, which has shown promising antiviral activity against some herpesviruses. Moreover, its amidic derivatives valpromide and valnoctamide also share this antiherpetic activity. This review summarizes the current research on the use of VPA and its amidic derivatives as alternatives to traditional antiherpetics in the fight against HSV infections.

The Use of Methotrexate in Rheumatoid Arthritis

1985 ◽  
Vol 19 (5) ◽  
pp. 349-358 ◽  
Author(s):  
Peter W. Letendre ◽  
Douglas J. DeJong ◽  
Donald R. Miller
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Folic Acid ◽  
Side Effects ◽  
Adverse Effects ◽  
Systemic Administration ◽  
Refractory Disease ◽  
Controlled Clinical Trials ◽  
Folic Acid Antagonist ◽  
Acid Antagonist

The use of methotrexate in rheumatoid arthritis is reviewed. Methotrexate, a folic acid antagonist, is sometimes employed in an attempt to symptomatically control patients whose disease does not respond adequately to conventional therapies. Systemic administration of 7.5–15 mg/wk in a “pulse” fashion appears to be effective without precipitating severe adverse effects. However, concern over potentially serious side effects and a lack of well-controlled clinical trials have limited its use to severe, refractory disease. Further studies are needed before its role in rheumatoid arthritis can justifiably be expanded.

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