Cytoprotective pyridinol antioxidants as potential therapeutic agents for neurodegenerative and mitochondrial diseases

Alam, Mohammad Parvez; Khdour, Omar M.; Arce, Pablo M.; Chen, Yana; Roy, Basab; Johnson, Walter G.; Dey, Sriloy; Hecht, Sidney M.

doi:10.1016/j.bmc.2014.06.040

Cited by 16 publications

(11 citation statements)

References 37 publications

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“…The compounds with exocyclic azetidine at position 2 ( 36 – 41 ) showed improved metabolic stability as reported for compounds 34 and 35 in the pyridinol series [ 99 ]. In addition, more sterically hindered ethers, such as that containing an isopropoxy moiety ( 39 ) at position 4, resulted in additional improvement of metabolic stability.…”

Section: Idebenone Analoguesmentioning

confidence: 86%

“…A series of regioisomeric pairs of pyridinol derivatives of compound 27 , with different side chain lengths and lacking of the hydroxyl group, was synthesized ( 28 – 33 ). In addition, the authors obtained compounds 34 and 35 by introducing a 16 carbon atoms side chain and an azetidine group at position 6 of the pyridinol redox core ( Figure 6 ) [ 99 ].…”

Section: Idebenone Analoguesmentioning

confidence: 99%

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Idebenone: Novel Strategies to Improve Its Systemic and Local Efficacy

et al. 2018

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The key role of antioxidants in treating and preventing many systemic and topical diseases is well recognized. One of the most potent antioxidants available for pharmaceutical and cosmetic use is Idebenone (IDE), a synthetic analogue of Coenzyme Q10. Unfortunately, IDE’s unfavorable physicochemical properties such as poor water solubility and high lipophilicity impair its bioavailability after oral and topical administration and prevent its parenteral use. In recent decades, many strategies have been proposed to improve IDE effectiveness in the treatment of neurodegenerative diseases and skin disorders. After a brief description of IDE potential therapeutic applications and its pharmacokinetic and pharmacodynamic profile, this review will focus on the different approaches investigated to overcome IDE drawbacks, such as IDE incorporation into different types of delivery systems (liposomes, cyclodextrins, microemulsions, self-micro-emulsifying drug delivery systems, lipid-based nanoparticles, polymeric nanoparticles) and IDE chemical modification. The results of these studies will be illustrated with emphasis on the most innovative strategies and their future perspectives.

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Section: Idebenone Analoguesmentioning

confidence: 86%

Section: Idebenone Analoguesmentioning

confidence: 99%

Idebenone: Novel Strategies to Improve Its Systemic and Local Efficacy

et al. 2018

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“…Ìíîãî÷èñëåííûå ñèíòåòè÷åñêèå ïðîèçâîäíûå ïè-ðèìèäèíîâ îáëàäàþò øèðîêèì ñïåêòðîì ôàðìàêîëî-ãè÷åñêîé àêòèâíîñòè è âîâëå÷åíû â ðåãóëÿöèþ èììóí-íîãî îòâåòà è ïðîöåññîâ ðåãåíåðàöèè [3,13,15]. Ëå-êàðñòâåííûå ïðîèçâîäíûå ïèðèìèäèíîâ ïðîÿâëÿþò êëèíè÷åñêóþ ýôôåêòèâíîñòü ïðè ëå÷åíèè îíêîëîãè÷å-ñêèõ, ïñèõîíåâðîëîãè÷åñêèõ çàáîëåâàíèé è òåðàïèè òðàâìàòè÷åñêèõ ñîñòîÿíèé [4,9].…”

Section: ââåäåíèåunclassified

“…Ëå-êàðñòâåííûå ïðîèçâîäíûå ïèðèìèäèíîâ ïðîÿâëÿþò êëèíè÷åñêóþ ýôôåêòèâíîñòü ïðè ëå÷åíèè îíêîëîãè÷å-ñêèõ, ïñèõîíåâðîëîãè÷åñêèõ çàáîëåâàíèé è òåðàïèè òðàâìàòè÷åñêèõ ñîñòîÿíèé [4,9]. Øèðîêèé ñïåêòð ôàðìàêîëîãè÷åñêîé àêòèâíîñòè è íèçêàÿ òîêñè÷íîñòü ñèíòåòè÷åñêèõ ïðîèçâîäíûõ ïèðèìèäèíîâ îïðåäåëÿ-þò àêòóàëüíîñòü ïîèñêà è ðàçðàáîòêè íîâûõ îðèãè-íàëüíûõ ëåêàðñòâåííûõ ñðåäñòâ â ðÿäó ïðîèçâîäíûõ ïèðèìèäèíîâ [5,9,10,13,15]. Ïîäîáíûé ñêðèíèíã â îòíîøåíèè 5-îêñèïèðèìèäèíîâ ïðîâîäèòñÿ ÔÃÁÍÓ "ÍÈÈ ôàðìàêîëîãèè èì.…”

Section: ââåäåíèåunclassified

“…Ñîãëàñíî äàí-íûì ëèòåðàòóðû, NKð46 ýêñïðåññèðóåòñÿ íà ïîâåðõ-íîñòè òîëüêî àêòèâèðîâàííûõ NK-êëåòîê [12,14], è èãðàåò öåíòðàëüíóþ ðîëü â ëèòè÷åñêîé àêòèâíîñòè NK-êëåòîê [13,14]. Èçâåñòíî, ÷òî NKp46 ÿâëÿåòñÿ ïåðâè÷íûì ðåöåïòîðîì êîíòðîëÿ îïóõîëåâîãî ïðîöåñ-ñà, êàê ó ìûøåé, òàê è ó äðóãèõ âèäîâ aeèâîòíûõ.…”

Section: ïðèìå÷àíèåunclassified

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Иммунофармакологические Свойства Нового Производного 5-Оксипиримидина Снк-411

Kuznetsova¹,

Таллерова²,

Никитин³

et al. 2015

Эксп. и клин. фармакол.

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Исследовано действие нового производного 5-оксипиримидина СНК-411 в дозах от 1 до 50 мг/кг на параметры иммунной системы у интактных мышей. СНК-411 в дозах 25 мг/кг и 50 мг/кг стимулировал показатели иммунного клеточного ответа в реакции гиперчувствительности замедленного типа и гуморального ответа в реакции пассивной гемагглютинации в среднем в 1,2 раза (p < 0,05). СНК-411 в дозе 50 мг/кг стимулировал фагоцитарную активность перитонеальных макрофагов в 1,2 раза (p < 0,05). СНК-411 в дозе 25 мг/кг увеличивает (p < 0,01) содержание цитотоксических Т-лимфоцитов CD3+CD8+ в крови в 2,3 раза, в дозе 50 мг/кг увеличивает количество CD3+CD8+ в печени и тимусе в 3,3 и 1,4 раза, соответственно (p < 0,01). СНК-411 в дозе 25 мг/кг увеличивает содержание естественных киллеров CD335+ в крови и печени в 1,9 и 1,4 раза, соответственно (p < 0,05).

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