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2011 | 38 | 2 | 117-144
Article title

Badania in silico w przewidywaniu zdolności przenikania leków przez barierę krew-mózg

Content
Title variants
EN
In silico prediction of blood-brain barrier penetration of drugs
Languages of publication
PL
Abstracts
EN
Blood-brain barrier (BBB) is a complex cellular system, which separates the brain and central nervous system (CNS) from the bloodstream. BBB permeability (BBBp) is one of the most important pharmacokinetic properties not only for CNS-active drugs. The brain penetration of CNS-nonactive drugs should be very low to minimize the unwanted CNS side effects. Determination of BBBp of therapeutic compounds is an important component in the design of drugs. Usually the blood-brain partition coefficient (log BB) is used to determine BBB permeability of chemical compounds. Quantitative structure-activity relationship (QSAR) models offer predicting log BB from the molecular structure of a compound. Experimental determination of log BB of the compound is difficult, labour-consuming and time-consuming. It is desirable to predict the blood-brain partition coefficient of compounds from their molecular structures or from physicochemical properties. Various descriptors have been revealed in many studies to be important for predicting BBBp of small molecules via passive diffusion. The most important descriptors usually used to build QSAR models and the QSAR modeling methods were presented in this work. The in silico models based on QSAR are frequently used, but are limited by the restricted accessibility of in vivo data during the early drug discovery phase.
PL
Bariera krew-mózg (ang. Blood-brain barrier - BBB) jest złożonym systemem, który oddziela ośrodkowy układ nerwowy (OUN) od krwioobiegu. Zdolność przenikania bariery krew-mózg (ang. Blood-brain barrier permeability – BBBp) stanowi jedną z najważniejszych właściwości farmakokinetycznych dla leków działających ośrodkowo. Równocześnie, poziom przenikania do mózgu leków działających poza OUN powinien być niski, dla uniknięcia ośrodkowych działań niepożądanych. Ustalenie BBBp substancji leczniczej jest ważnym elementem projektowania leków. Najczęściej używanym wskaźnikiem poziomu przenikania jest współczynnik rozdziału pomiędzy mózg i krew (log BB). Modele matematyczne ilościowej zależności pomiędzy strukturą i aktywnością (ang. quantitative structure-activity relationship - QSAR) dają możliwość przewidywania parametru log BB na podstawie badania struktury związku chemicznego. Doświadczalne ustalanie wartości log BB jest trudne, czasochłonne i pracochłonne. Bardzo przydatna jest więc możliwość przewidywania współczynnika rozdziału związku pomiędzy mózg i krew, na podstawie właściwości fizykochemicznych lub ich struktury. Znacząca rola różnych deskryptorów molekularnych w przewidywaniu log BB została udowodniona w wielu doświadczeniach. W niniejszej pracy opisano najważniejsze z parametrów, często używanych do tworzenia modeli QSAR oraz popularne metody modelowania QSAR. Stosowanie modeli in silico, opartych na metodach QSAR, jest bardzo rozpowszechnione. We wstępnej fazie poszukiwania leku użyteczność tych metod jest ograniczona brakiem dostępu do danych z badań in vivo.
Discipline
Publisher

Year
Volume
38
Issue
2
Pages
117-144
Physical description
Contributors
References
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paper
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bwmeta1.element.psjd-9aceedf5-4a05-422b-b377-99db939cd3b5
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