کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1370725 | 981828 | 2011 | 5 صفحه PDF | دانلود رایگان |
A number of 5′-O-fatty acyl derivatives of 2′,3′-didehydro-2′,3′-dideoxythymidine (stavudine, d4T) were synthesized and evaluated for anti-HIV activities against cell-free and cell-associated virus, cellular cytotoxicity, and cellular uptake studies. The conjugates were found to be more potent than d4T. Among these conjugates, 5′-O-12-azidododecanoyl derivative of d4T (2), displaying EC50 = 3.1–22.4 μM, showed 4- to 9-fold higher activities than d4T against cell-free and cell-associated virus. Cellular uptake studies were conducted on CCRF-CEM cell line using 5(6)-carboxyfluorescein derivatives of d4T attached through β-alanine (9) or 12-aminododecanoic acid (10) as linkers. The fluorescein-substituted analog of d4T with long chain length (10) showed 12- to 15-fold higher cellular uptake profile than the corresponding analog with short chain length (9). These studies reveal that conjugation of fatty acids to d4T enhances the cellular uptake and anti-HIV activity of stavudine.
The synthesis, anti-HIV activities against cell-free and cell-associated virus, cellular cytotoxicity, and cellular uptake studies of 5′-O-fatty acyl derivatives of 2′,3′-didehydro-2′,3′-dideoxythymidine (stavudine, d4T) are reported.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 7, 1 April 2011, Pages 1917–1921