Devraj R, Jurayj J, Fernandez J A, Barrett J F, Cushman M
Department of Medicinal Chemistry, School of Pharmacy, Purdue University, West Lafayette IN 47907, USA.
Anticancer Drug Des. 1996 Jun;11(4):311-24.
An array of novel 2-acyl-1,2-dihydroellipticines was prepared and evaluated for in vitro cytotoxicity in a variety of human cancer cell lines. The ellipticine analogs were also tested for inhibition of topoisomerase II in both decatenation and cleavable complex formation assays. Some of the new ellipticine derivatives were prepared by acylation of ellipticine with acid chlorides in tetrahydrofuran, followed by reduction of the intermediate 2-acylellipticinium ions with sodium cyanoborohydride. Others were synthesized by acylation of ellipticine with p-nitrophenyl chloroformate, reduction of the 2-acylellipticinium ion with sodium cyanoborohydride, and displacement of the p-nitrophenoxide anion with a variety of oxygen and nitrogen nucleophiles. The cytotoxicities of the new 2-acyl-1,2-dihydroellipticines varied widely, and correlated well with their topoisomerase II inhibitory activities.
制备了一系列新型的2-酰基-1,2-二氢玫瑰树碱，并在多种人类癌细胞系中评估了它们的体外细胞毒性。还在解连环和可裂解复合物形成试验中测试了玫瑰树碱类似物对拓扑异构酶II的抑制作用。一些新的玫瑰树碱衍生物是通过玫瑰树碱在四氢呋喃中与酰氯进行酰化反应，然后用氰基硼氢化钠还原中间产物2-酰基玫瑰树碱离子而制备的。其他的则是通过玫瑰树碱与对硝基苯基氯甲酸酯进行酰化反应，用氰基硼氢化钠还原2-酰基玫瑰树碱离子，并用各种氧和氮亲核试剂取代对硝基苯氧基阴离子来合成的。新型2-酰基-1,2-二氢玫瑰树碱的细胞毒性差异很大，并且与其拓扑异构酶II抑制活性密切相关。
