Facile exchange of the cyano group in highly potent anticancer cyanomorpholinyl anthracyclines.
Facile exchange of the cyano group in highly potent anticancer cyanomorpholinyl anthracyclines.
复制标题
高效抗癌氰基吗啉基蒽环类药物中氰基的轻松交换。
DOI：
10.1016/0006-2952(88)90742-3
复制
发表时间：
1988
影响因子：
5.8
通讯作者：
Thomas,DW
中科院分区：
文献类型：
--
作者：
Peters,JH;Gordon,GR;Nolen3rd,HW;Tracy,M;Thomas,DW
Materials and methodsThe anthracyclines, DXR, doxorubicinone(DXRONE), M-DXR, CM-DXR, and CM-DNR, were obtained from the sources reported previously [12]. N-(ZHydroxyethyl) DXR (HE-DXR) was reported on later [lo]. The KCN [14C](8.6 Ci/mol) was purchased from ICN Radiochemicals (Irvine, CA). Liquid chromatography (LC) of this material on a Nucleosil IOSB, 10 pm, 4.6 x 250 mm, strong anion exchange column (Alltech Associates, Inc., Deerfield, IL) at 30” using a mobile phase of 0.1 M sodium acetate buffer, pH 5.0, containing 0.2 M sodium perchlorate at 0.5 ml/min [13] and a radioactivity flow detector (model HP, Radiomatic Instruments & Chemical Co., Inc., Tampa, FL) yielded a principal peak at the elution position of CN-containing 97.6% of the total radioactivity. Separation of anthracyclines was accomplished using reverse-phase LC on a C-8 column (Ultrasphere octyl, 4.6 x 150 mm, 5 pm, Altex Scientific Operations, Berkeley, CA). The mobile phase (35% acetonitrile in 0.05 M phosphate buffer, pH 7.0) was pumped at a flow rate of 1.5 ml/min with detection and quantitation performed at 254 nm (model 1084B liquid chromatograph, Hewlett-Packard, Santa Clara, CA). The anthracyclines were resolved adequately and yielded the following sequence of retention times: DXR-ONE, 6.3 mitt; CM-DNR, 9.0 min (isomers not separated); diastereoisomers of CM-DXR, 10.1 and 11.1 min; HE-DXR, 15.1 mitt; DXR, 18.1 min; and M-DXR, 20.1 min.Incubation conditions were those employed for tests of the activity of anthracyclines against P388 tumor cells [2], viz. 400-500~ 1 of 25 mM 4-(2-hydroxyethyl)-l-piperazineethanesulfonic acid (HEPES) buffer, pH 7.3, with the added anthracycline in a few microliters of methanol and KCN114C1 or KCN in 0.01 N sodium hvdroxide. The total nanomol of anthracycline or KCN [14C] added are indicated in Table 1. After incubation for 1 hr at 37”, the sample was passed through a C-18 Sep-Pak cartridge (Waters Associates, Milford, MA) preconditioned with 2 ml of methanol and 5 ml water. The effluent liquid was collected and the cartridge was rinsed with 25 ml of water. The anthracyclines were stripped from the cartridge by elution with 4 ml of methanol. After evaporation of the methanol at room temperature under a stream of N,, we dissolved the residue in 400 1 of acetonitrile. Samples of this concentrated solution were employed for LC using the UV and radiochemical detectors in series.
