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  • Title: Cytotoxicity and topo I targeting activity of substituted 10--nitrogenous heterocyclic aromatic group derivatives of SN-38.
    Author: Li QY, Deng XQ, Zu YG, Lv H, Su L, Yao L, Zhang Y, Li L.
    Journal: Eur J Med Chem; 2010 Jul; 45(7):3200-6. PubMed ID: 20392545.
    Abstract:
    A series of 10-position substituted nitrogenous heterocyclic aromatic group derivatives of SN-38 were prepared. Most of these compounds possessed lower cytotoxicities than CPT. Compound 13 revealed potent cytotoxicity similar to CPT, and compounds 17, 18, and 19 showed similar cytotoxic activity to topotecan. All of the pyridine salt derivatives (7-16) revealed comparable or superior topo I inhibitory activity in relation to CPT. Ethyl in the 7-position of these compounds can increase the cytotoxicity and inhibitory activity to topo I compared with corresponding pyridine salts CPT derivatives (7a-13a) and simultaneously maintain good water solubility. This result is consistent with the SAR of CPT.
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