Wyniki wyszukiwania - Biblioteka Nauki

1

Konwergentna synteza analogów witamin D

100%

Kutner A.

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tom T. 85, nr 5

322-329

PL

Przedstawiono konwergentną strategię syntezy substancji farmaceutycznych z grupy witamin D, w której z tego samego kluczowego półproduktu otrzymuje się nie tylko główny naturalny metabolit witaminy D3, ale także jego analogi zmodyfikowane w alifatycznym łańcuchu bocznym. Analogi te są substancjami czynnymi leków lub nowymi związkami o potencjalnym działaniu terapeutycznym. Kluczowy półprodukt (C-22 alkohol witaminowy) jest obecnie otrzymywany z dostępnego handlowo ergocalciferolu, w wyniku wprowadzenia dodatkowej grupy hydroksylowej przy atomie węgla C-1 i usunięcia naturalnego łańcucha bocznego. Analogi są otrzymywane przez dołączenie do syntonu witaminowego oddzielnie otrzymanego fragmentu łańcucha bocznego. Konwergentna strategia syntezy stała się podstawą do opracowania w Instytucie Farmaceutycznym technologii wytwarzania substancji farmaceutycznych z grupy witamin D.

EN

A review with 47 refs. covers a convergent strategy for prepg. vitamin D group compds., based on one key intermediate (C-22 vitamin alc.) and affording not only the major vitamin D3 metabolite but also analogs modified at the aliphatic side chain. The analogs are active components in drugs or new compds. endowed with a therapeutic activity. The key intermediate is now prepd. from ergocalciferol. Analogs are prepd. by adding a side-chain fragment (prepd. sep.) to the vitamin synthon. The strategy is illustrated by syntheses of vitamin D2 and D3 analogs which may have a therapeutic value.

2

Side-chain modified vitamin D analogs require activation of both PI 3-K and erk1,2 signal transduction pathways to induce differentiation of human promyelocytic leukemia cells

63%

Marcinkowska E. , Kutner A.

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nr 2

EN

Synthetic analogs of vitamin D for potential use in differentiation therapy should selectively regulate genes necessary for differentiation without inducing any perturbations in calcium homeostasis. PRI-1906, an analog of vitamin D2, and PRI-2191, an analog of vitamin D3 bind nuclear vitamin D receptor (nVDR) with substantially lower affinity than 1,25-dihydroxyvitamin D3 (1,25-D3), but have higher differentiation-inducing activity as estimated in HL-60 leukemia cell model. To examine how their increased differentiation-inducing activity is regulated we tested the hypothesis that membrane-mediated events, unrelated to nVDR, take part in the differentiation in response to PRI-1906 and PRI-2191. The induction of leukemia cell differentiation in response to the analogs of vitamin D was inhibited by LY294002 (phosphatidyl- inositol 3-kinase inhibitor), PD98059 (inhibitor of MEK1,2, an upstream regulator of extracellular-signal regulated kinase) and rapamycin (p70 S6K inhibitor) pointing out that activation of signal transduction pathways unrelated to nVDR is necessary for differentiation. On the other hand, inhibition of cytosolic phospholipase A2 accelerated the differentiation of HL-60 cells induced by either 1,25-D3 or by the vitamin D analogs suggesting possible existence of a feedback loop between extracellular-signal regulated kinases and phospholipase A2.

3

Technologie syntezy metabolitów i analogów witamin D. Dokonania i perspektywy

51%

Ryznar T. , Krupa M. , Kutner A.

Przemysł Chemiczny

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2002

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tom T. 81, nr 5

300-310

4

Modyfikacja nowej metody otrzymywania kalcypotriolu

45%

Chodyński M. , Fitak H. , Leszczyńska K. , Żochowski J. , Kutner A.

Przemysł Chemiczny

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2007

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tom T. 86, nr 8

760-763

5

Ekonomiczna metoda otrzymywania dokserkalcyferolu

45%

Chodyński M. , Fitak H. , Krajewski K. , Leszczyńska K. , Kutner A.

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tom T. 87, nr 7

800-803

6

An involvement of phoshatidylinositol 3-kinase in anti-apoptotic action of l,25-dihydroxyvitamin D3 and its low-calcemic analogues in SH-SY5Y celi line

45%

Regulska M. , Leskiewicz M. , Budzszewska B. , Kutner A. , Lason W.

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tom 66

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nr 4

7

Polimorfizm maleinianu rosiglitazonu : fakty i mity

38%

Chodyński M. , Fitak H. , Glice M. M. , Korczak K. , Leszczyńska K. , Kutner A.

Przemysł Chemiczny

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2007

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tom T. 86, nr 8

756-759

8

Pretreatment is not mandatory for neuroprotection with 1alpha,25-dihydroxyvitamin D3 in perinatal hypoxic-ischemic rat brain damage in vivo and in excitotoxic injury of primary neuronal cell cultures

32%

Makarewicz D. , Kajta M. , Zieminska E. , Jantas D. , Domin H. , Lason W. , Kutner A. , Lazarewicz J. W.

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nr 1

EN

Previous in vivo and in vitro studies demonstrated neuroprotective potential of pretreatment with 1α, 25-dihydroxyvitamin D3 (calcitriol). The aim of present study was to determine effectiveness of calcitriol administered in vivo after brain ischemic episode in the rat model of perinatal asphyxia, or co-applied with some delay during 24 h exposure to glutamate of the mice hippocampal, cortical and cerebellar neuronal cultures at 7th and 12th day in vitro. In some experiments calcitriol was given after acute exposure to glutamate of the rat cerebellar neurons. Our results demonstrated, that in the 7 day old rat pups submitted to hypoxia ñ ischemia acute application of calcitriol in one dose of 2 μg/kg 30 min after termination of the insult or sub-chronic, 7-day post-treatment with calcitriol effectively diminished brain damage. The rate of such accomplished neuroprotection exceeded that achieved by hypoxic preconditioning, used as the reference neuroprotective method. Moreover the results of our in vitro experiments revealed the ability of calcitriol to reduce excitotoxicity in a way dependent on origin of neuronal cells, stage of their development and duration of excitotoxic insult. Calcitriol was neuroprotective when it was applied together with glutamate or even with up to 6 h delay during 24-h excitotoxic challenge to the hippocampal and neocortical, but not cerebellar neuronal cultures. In addition calcitriol inhibited glutamate-induced caspase-3 activity in hippocampal cultures. We ascribe these protective effects of calcitriol to a rapid, possibly non-genomic modulation by this compound of the mechanisms that are instrumental in its direct neuroprotective action. The study was supported by Polish MNSW Scientifi c Network Fund no 26/E-40/SN-0023/2007