Marastoni M, Bazzaro M, Bortolotti F, Salvadori S, Tomatis R
Department of Pharmaceutical Sciences and Biotecnology Centre, University of Ferrara, Ferrara, Italy.
Eur J Med Chem. 1999 Jul-Aug;34(7-8):651-7. doi: 10.1016/s0223-5234(00)80034-3.
Two series of peptidomimetics containing a novel C(2) pseudosymmetrical hydroxyalkyldiamino core structure were prepared from amino acid starting materials and tested for inhibitory activity against the HIV-1 protease (HIV-1 Pr) and the virus in cell culture. In the 2,3-diamino-1-hydroxypropane series, compound 6a, containing P1/P1(I) benzyl and P2/P2(I) Fmoc substituents, displayed modest HIV-1 Pr inhibition (IC(50) = 430 nM). The corresponding 2,4-diamino-1-hydroxybutane derivative (6b) was the best inhibitor of the series (IC(50) = 160 nM). Interestingly, 6a and 6b showed satisfactory inhibition of HIV replication in cell culture (ED(50) = 340 and 110 nM, respectively), a result which suggests good cell membrane penetration by this class of compounds.
从氨基酸起始原料制备了含有新型C(2) 假对称羟基烷基二氨基核心结构的两系列拟肽，并在细胞培养中测试了它们对HIV-1蛋白酶（HIV-1 Pr）和病毒的抑制活性。在2,3-二氨基-1-羟基丙烷系列中，含有P1/P1(I)苄基和P2/P2(I) Fmoc取代基的化合物6a对HIV-1 Pr表现出适度的抑制作用（IC(50) = 430 nM）。相应的2,4-二氨基-1-羟基丁烷衍生物（6b）是该系列中最佳的抑制剂（IC(50) = 160 nM）。有趣的是，6a和6b在细胞培养中对HIV复制表现出令人满意的抑制作用（ED(50)分别为340和110 nM），这一结果表明这类化合物具有良好的细胞膜穿透性。
