Radi Marco, Adema Auke D, Daft Jonathan R, Cho Jong H, Hoebe Eveline K, Alexander Lou-Ella M M, Peters Godefridus J, Chu Chung K
The University of Georgia College of Pharmacy, Athens, Georgia 30602, USA.
J Med Chem. 2007 May 3;50(9):2249-53. doi: 10.1021/jm0612923. Epub 2007 Apr 10.
l-1,3-Dioxolane-cytidine, a potent anticancer agent against leukemia, has limited efficacy against solid tumors, perhaps due to its hydrophilicity. Herein, a library of prodrugs were synthesized to optimize in vitro antitumor activity against non-small cell lung cancer. N4-Substituted fatty acid amide prodrugs of 10-16 carbon chain length demonstrated significantly improved antitumor activity over l-1,3-dioxolane-cytidine. These in vitro results suggest that the in vivo therapeutic efficacy of l-1,3-dioxolane-cytidine against solid tumors may be improved with prodrug strategies.
L-1,3-二氧戊环胞苷是一种有效的抗白血病抗癌药物，但对实体瘤的疗效有限，这可能归因于其亲水性。在此，合成了一系列前药以优化对非小细胞肺癌的体外抗肿瘤活性。碳链长度为10 - 16的N4-取代脂肪酸酰胺前药比L-1,3-二氧戊环胞苷表现出显著提高的抗肿瘤活性。这些体外实验结果表明，前药策略可能会提高L-1,3-二氧戊环胞苷对实体瘤的体内治疗效果。
