Breast anticancer drug tamoxifen and its metabolites bind DNA and RNA at multiple sites
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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 content...
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.
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