Design, synthesis, antiviral activity, and pre-formulation development of poly-L-arginine-fatty acyl derivatives of nucleoside reverse transcriptase inhibitors.
Design, synthesis, antiviral activity, and pre-formulation development of poly-L-arginine-fatty acyl derivatives of nucleoside reverse transcriptase inhibitors.
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DOI：
10.1080/15257770.2014.945649
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Parang K
中科院分区：
文献类型：
--
作者：
Pemmaraju BP;Malekar S;Agarwal HK;Tiwari RK;Oh D;Doncel GF;Worthen DR;Parang K
本工作的目的是设计抗HIV核苷与脂肪酸和细胞穿透聚-L-精氨酸（polyArg）肽的缀合物。合成了三种聚精氨酸细胞穿透肽与阿洛夫定（FLT）、拉米夫定（3 TC）和恩曲他滨（FTC）的脂肪酰基衍生物的缀合物。一般而言，化合物对X4和R5无细胞病毒表现出抗HIV活性，EC 50值为1.5-16.6 μM。FLT-CO-（CH 2）12-CO-（Arg）7对X4和R5无细胞病毒的EC 50值分别为2.9 μM和3.1 μM。通过测定溶液状态降解和脂溶性，选择FLT结合物进行进一步的处方前研究。发现该化合物在中性和氧化条件下稳定，在加热条件下中等稳定。
The objective of this work was to design conjugates of anti-HIV nucleosides conjugated with fatty acids and cell penetrating poly-L-arginine (polyArg) peptides. Three conjugates of polyArg cell-penetrating peptides with fatty acyl derivatives of alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC) were synthesized. In general, the compounds exhibited anti-HIV activity against X4 and R5 cell-free virus with EC50 values of 1.5–16.6 μM. FLT-CO-(CH2)12-CO-(Arg)7 exhibited EC50 values of 2.9 μM and 3.1 μM against X4 and R5 cell-free virus, respectively. The FLT conjugate was selected for further preformulation studies by determination of solution state degradation and lipid solubility. The compound was found to be stable in neutral and oxidative conditions and moderately stable in heated conditions.
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影响因子：
82.9
作者：
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通讯作者：
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影响因子：
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