Ïðîâåäåíî èññëåäîâàíèå âëèÿíèÿ ïðîèçâîäíîãî ïèððîëà 5-àìèíî-4-(1,3-áåíçîòèà-çîë-2-èí)-1-(3-ìåòîêñèôåíèë)-1,2-äèãèäðî-3Í-ïèððîë-3-îíà (Ä1) íà ñîñòîÿíèå îðãàíîâ âåðõíåãî îòäåëà aeåëóäî÷íî-êèøå÷íîãî òðàêòà (aeåëóäêà è òîùåé êèøêè) è ïå÷åíè ïðè 1,2-äèìåòèëãèäðàçèí-èíäóöèðîâàííîì ðàêå òîëñòîãî êèøå÷íèêà êðûñ. Ïîêàçàíî îòñóòñò-âèå âûðàaeåííîé òîêñè÷íîñòè èññëåäóåìîãî ñîåäèíåíèÿ ïî îòíîøåíèþ ê óêàçàííûì îðãà-íàì. Îáíàðóaeåíî, ÷òî â óñëîâèÿõ êàíöåðîãåíåçà Ä1 îêàçûâàåò çàùèòíîå äåéñòâèå, óìåíü-øàÿ âîñïàëåíèå è ñïîñîáñòâóÿ íîðìàëèçàöèè ìîðôîôóíêöèîíàëüíîé àêòèâíîñòè ñëèçè-ñòîé îáîëî÷êè aeåëóäêà è òîùåé êèøêè êðûñ. Ä1 òàêaeå íå óñóãóáëÿåò ïîâðåaeäåíèÿ ïå÷åíè, âûçâàííûå êàíöåðîãåíîì, õîòÿ è íå ÿâëÿåòñÿ ãåïàòîïðîòåêòîðîì.Êëþ÷åâûå ñëîâà: ïðîèçâîäíîå ïèððîëà; ðàê òîëñòîãî êèøå÷íèêà; aeåëóäîê; òîùàÿ êèøêà; ïå÷åíü. ÂÂÅÄÅÍÈÅÂàaeíûì êðèòåðèåì ïðè ðàçðàáîòêå ïðîòèâîîïóõîëå-âîãî ëåêàðñòâåííîãî ñðåäñòâà íà îñíîâå äåéñòâóþùåãî âåùåñòâà ÿâëÿåòñÿ, íàðÿäó ñ åãî ýôôåêòèâíîñòüþ, îòñóò-ñòâèå îòðèöàòåëüíîãî âëèÿíèÿ íà ñîñòîÿíèå îðãàíèçìà ïðè äëèòåëüíîì ïðèìåíåíèè. Îðãàíû ïèùåâàðåíèÿ ïåð-âûìè ïîäâåðãàþòñÿ âîçäåéñòâèþ âåùåñòâ ýêçîãåííîãî ïðîèñõîaeäåíèÿ, â òîì ÷èñëå ëåêàðñòâåííûõ ïðåïàðàòîâ, ïðè èõ ïåðîðàëüíîì ïðèìåíåíèè, è èìåííî ñî ñòîðîíû ïèùåâàðèòåëüíîé ñèñòåìû íàáëþäàåòñÿ áîëüøèíñòâî ïîáî÷íûõ ýôôåêòîâ ïðîòèâîîïóõîëåâîé òåðàïèè. Ýòî ñâÿçàíî ñ ïîâûøåííîé ÷óâñòâèòåëüíîñòüþ ýïèòåëèÿ aeå-ëóäî÷íî-êèøå÷íîãî òðàêòà (AEÊÒ) ê âîçäåéñòâèþ öèòî-ñòàòèêîâ âñëåäñòâèå åãî âûñîêîé ïðîëèôåðàòèâíîé àê-òèâíîñòè [9], à òàêaeå ñ óÿçâèìîñòüþ ïå÷åíè, îáåñïå÷è-âàþùåé ïðîöåññû äåòîêñèêàöèè êñåíîáèîòèêîâ [15].Íàèáîëåå ðàñïðîñòðàíåííûì ìåòîäîì ëå÷åíèÿ íå-îïëàçèé ÿâëÿåòñÿ õèìèîòåðàïèÿ, êîòîðàÿ îáëàäàåò âûñî-êîé ÷àñòîòîé ïîáî÷íûõ ýôôåêòîâ [9].  ïîñëåäíåå âðåìÿ ïðèâëåêàþò âíèìàíèå èíãèáèòîðû ïðîòåèíêèíàç êàê ñïåöèôè÷åñêèå èíãèáèòîðû ïðîëèôåðàòèâíîé àêòèâíî-ñòè, îáëàäàþùèå ñïåöèôè÷åñêèì âîçäåéñòâèåì íà òðàíñôîðìèðîâàííûå êëåòêè è íåçíà÷èòåëüíîé òîêñè÷-íîñòüþ ïî îòíîøåíèþ ê íîðìàëüíûì êëåòêàì îðãàíèç-ìà. Îäíàêî èíôîðìàöèÿ îá èõ ñèñòåìíîì âîçäåéñòâèè ïðîòèâîðå÷èâà [3], ÷òî òðåáóåò äåòàëüíûõ èññëåäîâàíèé â êàaeäîì êîíêðåòíîì ñëó÷àå. Îñîáåííî ýòî êàñàåòñÿ íèçêîìîëåêóëÿðíûõ èíãèáèòîðîâ ïðîòåèíêèíàç, ïåð-ñïåêòèâíûõ âñëåäñòâèå óìåðåííîé ñïåöèôè÷íîñòè, ïðåäïîëàãàþùåé øèðîêèé ñïåêòð çëîêà÷åñòâåííûõ "ìèøåíåé", óäîáñòâà ïðèìåíåíèÿ (âîçìîaeíîñòü ïåðî-ðàëüíîãî ââåäåíèÿ) è ìåíüøåé ñòîèìîñòè, ïî ñðàâíå-íèþ ñ ìîíîêëîíàëüíûìè àíòèòåëàìè [5].  êà÷åñòâå òàêèõ âåùåñòâ ïðèâëåêàþò âíèìàíèå ïðîèçâîäíûå ïèð-ðîëà, ñèíòåçèðîâàííûå ïîñëå in silico äèçàéíà Íàó÷-íî-ïðîèçâîäñòâåííûì õèìèêî-áèîëîãè÷åñêèì öåíòðîì Êèåâñêîãî íàöèîíàëüíîãî óíèâåðñèòåòà èì. Òàðàñà Øåâ÷åíêî [2].  ÷àñòíîñòè, âûñîêàÿ öèòîñòàòè÷åñêàÿ àêòèâíîñòü in vitro áûëà óñòàíîâëåíà äëÿ ñîåäèíåíèÿ 5-àìèíî-4-(1,3-áåíçîòèàçîë-2-èë)-1-(3-ìåòîêñèôå-íèë)-1,2-äèãèäðî-3Í-ïèððîë-3-îíà (äàëåå Ä1) (ðèñ. 1) [2]. Ýòî ñîåäèíåíèå îáëàäàåò ïðîòèâîîïóõîëåâîé àêòèâ-íîñòüþ, ñðàâíèìîé ñ òàêîâîé êëàññè÷åñêîãî ïðåïàðàòà 5-ôòîð-óðàöèëà [12].Èñõîäÿ èç ýòîãî, öåëüþ íàøåé ðàáîòû ÿâëÿåòñÿ èçó-÷åíèå âîçäåéñòâèÿ ïðîèçâîäíîãî ïèððîëà Ä1 íà ñëèçè-ñòóþ îáîëî÷êó aeåëó...
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