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MeSH: kyselina valproová-analogy a deriváty

8 záznamů v PubMed Filtry

Článek

A potential method to improve the in vitro cytotoxicity of half-sandwich Os(ii) complexes against A2780 cells

Dalton transactions (Cambridge, England. 2018 Apr 24 ; 47 (16) : 5714-5724.

Dalton Trans
ISSN 1477-9234 | 1477-9226
Zdroj

The [Os(η6-pcym)(dpa)(VP)]PF6 (1-VP) complex contains the histone deacetylase (HDAC) inhibitor valproate (2-propylpentanoate; VP) as a monodentate O-donor ligand and shows ca. 3-fold higher in vitro cytotoxicity against A2780 human ovarian carcinoma cells than its chlorido analogue [Os(η6-pcym)(dpa)Cl]PF6 (1-Cl); pcym = 1-methyl-4-(propan-2-yl)benzene (p-cymene), dpa = 2,2'-dipyridylamine. The complex 1-VP showed promising selectivity towards the A2780 ovarian carcinoma cell line (IC50 = 20.9 μM) over normal human hepatocytes (IC50 > 200.0 μM). Moreover, the complex 1-VP was found to be inactive against MCF-7 (breast adenocarcinoma), PANC-1 (pancreatic adenocarcinoma) and HT-29 (colon carcinoma) up to a concentration of 100 μM. Detailed flow cytometry studies indicated that treatment of A2780 cells with complex 1-VP led to induction of apoptosis, production of reactive oxygen species (ROS) and superoxide (SO) anion radicals, as well as mitochondrial membrane potential depletion and cell cycle perturbations. The microscopic assessment (standard hematoxylin/eosin staining) revealed signs of morphological changes associated with the progression of apoptosis in A2780 cells treated with the IC50 concentration of the complex 1-VP. Consistent with the intracellular production of ROS and SO, the complex 1-VP induced hydroxyl radical formation, as proved by EPR spin trapping experiments. This case study suggests that replacement of the chlorido ligand of half-sandwich Os(ii) complexes by a releasable monodentate biologically active ligand (e.g., VP used in this study) is an effective strategy for the development of novel non-platinum cytotoxic agents.

MeSH
2,2'-dipyridyl analogy a deriváty chemie MeSH
apoptóza účinky léků MeSH
cymeny MeSH
inhibiční koncentrace 50 MeSH
komplexní sloučeniny chemická syntéza chemie farmakologie MeSH
kyselina valproová analogy a deriváty chemie MeSH
lidé MeSH
mitochondriální membrány účinky léků MeSH
monoterpeny chemie MeSH
nádorové buněčné linie MeSH
osmium chemie MeSH
protinádorové látky chemická syntéza chemie farmakologie MeSH
reaktivní formy kyslíku metabolismus MeSH
superoxidy metabolismus MeSH
viabilita buněk účinky léků MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
Názvy látek
2,2'-dipyridyl MeSH
2,2'-dipyridylamine MeSH Prohlížeč
4-cymene MeSH Prohlížeč
cymeny MeSH
komplexní sloučeniny MeSH
kyselina valproová MeSH
monoterpeny MeSH
osmium MeSH
protinádorové látky MeSH
reaktivní formy kyslíku MeSH
superoxidy MeSH

Článek

Derivatives of valproic acid are active against pentetrazol-induced seizures in immature rats

Epilepsy research. 2013 Sep ; 106 (1-2) : 64-73. [epub] 20130628

Epilepsy Res
ISSN 1872-6844 | 0920-1211
Zdroj

Propylisopropyl acetamide (PID) and valnoctamide (VCD) are two CNS-active constitutional isomers of valproic acid (VPA) corresponding amide (and prodrug) valpromide. VPA is a major antiepileptic drug (AED) used also in children. Consequently, the purpose of the current study was to see if PID, VCD and two of VCD stereoisomers are active also in juvenile anticonvulsant animal seizure models. Rat pups 7, 12, 18 and 25 days old were pretreated with PID, VCD or the VCD stereoisomers (2S,3S)-VCD, and (2R,3S)-VCD and 30 min later pentetrazol (100mg/kg s.c.) was administered. The incidence of seizures, their expression pattern and their latencies were registered and the severity was expressed by means of a five-point scale. All four tested compounds exhibited anticonvulsant activity against generalized tonic-clonic seizures. Lower doses suppressed specifically the tonic phase in 7-, 12- and 18-day-old rats, while higher doses abolished both phases of generalized seizures. This effect was most pronounced in 12-day-old rats. Twenty-five-day-old rats exhibited suppression of the entire pattern of generalized seizures. There were no significant differences among the drugs used. The CNS-active amide derivatives of VPA, VCD (racemate or individual stereoisomers) and PID exhibit potent anticonvulsant activity against generalized convulsive seizures in developing rats. The majority of these developmental effects are quantitative; while a specific selective action on the tonic phase of generalized seizures is the main qualitative change found in our study.

Klíčová slova
Convulsive seizures, Derivatives of valproic acid, Immature rats, Pentetrazol,
MeSH
alylisopropylacetamid analogy a deriváty farmakologie MeSH
amidy farmakologie MeSH
antikonvulziva farmakologie MeSH
epilepsie generalizovaná chemicky indukované prevence a kontrola MeSH
konvulziva * MeSH
krysa rodu Rattus MeSH
kyselina valproová analogy a deriváty farmakologie MeSH
pentylentetrazol * MeSH
potkani Wistar MeSH
stárnutí fyziologie MeSH
stereoizomerie MeSH
záchvaty chemicky indukované prevence a kontrola MeSH
zvířata MeSH
Check Tag
krysa rodu Rattus MeSH
mužské pohlaví MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Názvy látek
alylisopropylacetamid MeSH
amidy MeSH
antikonvulziva MeSH
konvulziva * MeSH
kyselina valproová MeSH
pentylentetrazol * MeSH
propylisopropylacetamide MeSH Prohlížeč
valnoctamide MeSH Prohlížeč

Článek

Valproic acid, a molecular lead to multiple regulatory pathways

Folia biologica. 2007 ; 53 (2) : 37-49.

Folia Biol (Praha)
ISSN 0015-5500
Zdroj

Valproic acid (2-propyl pentanoic acid) is a drug used for the treatment of epilepsy and bipolar disorder. Although very rare, side effects such as spina bifida and other defects of neural tube closure indicate that valproic acid interferes with developmental regulatory pathways. Recently obtained data show that valproic acid affects cell growth, differentiation, apoptosis and immunogenicity of cultured cancer cells and tumours. Focused studies uncovered the potential of valproic acid to interfere with multiple regulatory mechanisms including histone deacetylases, GSK3 alpha and beta, Akt, the ERK pathway, the phosphoinositol pathway, the tricarboxylic acid cycle, GABA, and the OXPHOS system. Valproic acid is emerging as a potential anticancer drug and may also serve as a molecular lead that can help design drugs with more specific and more potent effects on the one side and drugs with wide additive but weaker effects on the other. Valproic acid is thus a powerful molecular tool for better understanding and therapeutic targeting of pathways that regulate the behaviour of cancer cells.