Slibné antikonvulzivum N-[(2,4-dichlorfenyl) methyl]-2-(2,4-dioxo-1H-chinazolin-3-yl) acetamid: studium působení v závislosti na dávce a hodnocení spektra antikonvulzivního účinku in vivo a in silico

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Autoři: Sergiy Shtrygol; Sergiy Zalevskyi; Mariia Mishchenko; Diana Shtrygol; Hanna Severina; Wassim El Kayal; Victoriya Georgiyants
Vyšlo v časopise: Čes. slov. Farm., 2022; 71, 224-233
Kategorie: Původní práce
doi: https://doi.org/https://doi.org/10.5817/CSF2022-5-224

Souhrn

Bylo studováno antikonvulzivní spektrum původního slibného antikonvulziva N-[(2,4-dichlorfenyl) methyl]-2-(2,4-dioxo-1H-chinazolin-3-yl) acetamidu. Sloučenina vykazovala výrazný antikonvulzivní účinek a významně snižovala mortalitu myší na modelech záchvatů vyvolaných pentylenetetrazolem, pikrotoxinem, strychninem a kofeinem. Na modelu záchvatů vyvolaných thiosemikarbazidem testovaná sloučenina mortalitu nesnížila. Získané výsledky naznačily, že mechanismus antikonvulzivního účinku zahrnuje GABA-ergní (účinnost v modelech záchvatů vyvolaných pentylenetetrazolem a pikrotoxinem), glycinergní (účinnost v modelu paroxyzmů vyvolaných strychninem) a adenosynergní (účinnost v modelu záchvatů vyvolaných kofeinem). Molekulární dokování slibného antikonvulziva k antikonvulzivním biologickým cílům bylo v souladu s mechanismy chemoindukovaných záchvatů, konkrétně GABA, glycinu a adenosinových receptorů typu A₂A, GABA_AT a enzymů BCAT. Byla zjištěna shoda mezi výsledky studií in vivo a in silico.

Klíčová slova:

dávka – chinazolin – acetamid – antikonvulzivní účinek – GABA receptor – A2A receptor – Gly receptor – dokování

Zdroje

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