Inouye Y, Kanamori T, Yoshida T, Bu X, Shionoya M, Koike T, Kimura E
Institute of Pharmaceutical Science, Hiroshima University School of Medicine, Japan.
Biol Pharm Bull. 1994 Feb;17(2):243-50. doi: 10.1248/bpb.17.243.
The macrocyclic polyamines, cyclen and cyclam, and their derivatives have been tested for inhibitory activity against the cytopathogenic effect (CPE) of human immunodeficiency virus type 1 strain HTLV-IIIB (HIV-1IIIB) on CD4+ human lymphoblastoma MT-4 cells. Cyclam and its derivatives were complexed with a variety of transition metal ions NiII, ZnII, CuII, FeIII and CoIII. The divalent metal complexes effected lower toxicity and greater anti-HIV-1 activity, while the trivalent metal complexes had no effect on HIV-1-dependent CPE. When dimerized, the anti-HIV activity of monomers was significantly enhanced. A potent inhibition of CPE by biscyclam was transiently observed 4 d after the virus infection, but was not seen at 6 d due to severe toxicity. The toxicity of biscyclam, referred to as delayed toxicity, could be overcome by a metal complexation. The strain specificities of biscyclams were further studied by testing their effects on syncytium formation between HIV-infected and uninfected human acute lymphoblastic leukemia MOLT-4 cells. The 50% inhibitory concentrations of biscyclams against HIV-2GH-1-dependent syncytium formation were less than one hundredth those for the other HIV strains (HIV-1IIIB, HIV-1RF and HIV-1SF-2).
大环多胺、环楞胺和环糊精及其衍生物已被测试对人类免疫缺陷病毒1型HTLV-IIIB株（HIV-1IIIB）在CD4+人淋巴瘤MT-4细胞上的细胞病变效应（CPE）的抑制活性。环糊精及其衍生物与多种过渡金属离子NiII、ZnII、CuII、FeIII和CoIII络合。二价金属络合物具有较低的毒性和较高的抗HIV-1活性，而三价金属络合物对HIV-1依赖的CPE没有影响。二聚化后，单体的抗HIV活性显著增强。双环糊精对CPE的有效抑制在病毒感染后4天短暂观察到，但在6天时由于严重毒性而未观察到。双环糊精的毒性，称为延迟毒性，可以通过金属络合来克服。通过测试双环糊精对HIV感染和未感染的人急性淋巴细胞白血病MOLT-4细胞之间合胞体形成的影响，进一步研究了其菌株特异性。双环糊精对HIV-2GH-1依赖的合胞体形成的50%抑制浓度不到其他HIV菌株（HIV-1IIIB、HIV-1RF和HIV-1SF-2）的百分之一。
