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Surveillance électrochimique, spectroscopique et théorique des interactions des anthracyclines avec l'ADN et l'acide ascorbique en adoptant deux voies: Études de lignées de cellules cancéreuses.

Les interactions pharmacodynamiques de trois antibiotiques anthracyclines, à savoir la doxorubicine (DXH), l’épirubicine (EpiDXH) et la daunorubicine (DNR) avec l’ADN en présence et absence d’acide ascorbique (AA) en tant qu’additif naturel ont été surveillées dans des conditions physiologiques (pH = 7,4, 4,7 et T = 309,5K). La Route-1 (Anthracycline-AA-ADN) et la Route-2 (Anthracycline-ADN-AA) ont été adoptées pour observer le comportement interactionnel par voltamétrie cyclique (CV) et spectroscopie UV-visible. En comparaison avec Route-2; Les réponses voltamétriques et spectrales ainsi que les valeurs de constante de liaison (Kb) et de changement d'énergie libre de Gibb (DeltaG) ont révélé une interaction plus forte et plus favorable du complexe anthracycline-AA avec l'ADN via la Route-1. Kb, s (taille des sites de liaison) et DeltaG évalués à partir de résultats expérimentaux (CV, UV-Vis) et théoriques (ancrage moléculaire) ont montré une force de liaison accrue des complexes tertiaires par rapport aux complexes médicament binaire-ADN. Les résultats ont été trouvés comparativement meilleurs à pH 7,4. La cohérence a été observée dans les paramètres de liaison évalués à partir de techniques expérimentales et théoriques. Les coefficients de diffusion (Do) et la constante de vitesse de transfert d'électrons hétérogène (ks, h) ont confirmé la formation de complexes via une cinétique de diffusion lente. Le pourcentage d'inhibition cellulaire (% Cinh) d'anthracyclines pour les lignées cellulaires cancéreuses non à petites cellules (NSCCL) H-1299 et H-157 a été évalué plus élevé en présence d'AA, complétant ainsi les résultats expérimentaux et théoriques.


Source: https://www.ncbi.nlm.nih.gov/pubmed/30372448


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