Breast anticancer drug tamoxifen and its metabolites bind DNA and RNA at multiple sites - Tajmir-Riahi, Heidar-Ali
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Tamoxifen is a breast anticancer drug that has been in worldwide use for the treatment of estrogen receptor (ER)-positive breast cancer for over 30 years. We compare the binding sites of the tamoxifen and its metabolites 4-hydroxytamoxifen and endoxifen with DNA and tRNA. Structural models showed that tamoxifen and its metabolites bind DNA and tRNA at multiple sites via hydrophobic, hydrophilic and H-bonding contacts with tRNA forming more stable drug conjugates than DNA. Drug conjugation did not alter DNA and tRNA conformations, while major biopolymer aggregation occurred at high drug…mehr

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Produktbeschreibung
Tamoxifen is a breast anticancer drug that has been in worldwide use for the treatment of estrogen receptor (ER)-positive breast cancer for over 30 years. We compare the binding sites of the tamoxifen and its metabolites 4-hydroxytamoxifen and endoxifen with DNA and tRNA. Structural models showed that tamoxifen and its metabolites bind DNA and tRNA at multiple sites via hydrophobic, hydrophilic and H-bonding contacts with tRNA forming more stable drug conjugates than DNA. Drug conjugation did not alter DNA and tRNA conformations, while major biopolymer aggregation occurred at high drug contents. The drug loading efficacy is correlated with the mechanism of action of antitumor activity of tamoxifen and its metabolites.
Autorenporträt
H.A. Tajmir-Riahi : Professeur de recherche à l'Université du Québec à Trois-Rivières (UQTR), Canada. Il a été admis au Cercle d'excellence de l'Université du Québec en 2017. Il a publié 340 articles dans des revues internationales, 6 livres et 15 chapitres de livres. Intérêt de recherche : interactions des médicaments avec l'ADN, l'ARN et les protéines ; délivrance de médicaments.