Antony A, Ramakrishnan T, Mikelens P, Jackson J, Levinson W
Bioinorg Chem. 1978 Jul;9(1):23-34. doi: 10.1016/s0006-3061(00)82003-7.
The copper complex of the antituberculous drug, insonicotinic acid hydrazide (INH), inhibits the RNA-dependent DNA polymerase of Rous sarcoma virus and inactivates its ability to malignantly transform chick embryo cells. The INH-copper complex binds to the 70S genome RNA of Rous sarcoma virus (RSV), which may account for its ability to inhibit the RNA-dependent DNA polymerase. The complex binds RNA more effectively than DNA in contrast to M-IBT-copper complexes, which bind both types of nucleic acids equally. The homopolymers, poly rA and poly rU, are bound by the INH-copper complex to a greater extent than poly rC. Isonicotinic acid hydrazide alone and CuSO4 alone bind neither DNA, RNA, poly (rA), poly (rU), nor poly (rC). However, CuSO4 alone binds poly (rI); INH alone does not. In addition to viral DNA synthesis, chick-embryo cell DNA synthesis is inhibited by the INH-copper complex. The extent of inhibition of cellular DNA synthesis is greater than that of cellular RNA and protein synthesis. No selective inhibition of transformation in cells previously infected with Rous sarcoma virus is observed.
抗结核药物异烟肼（INH）的铜配合物可抑制劳氏肉瘤病毒的RNA依赖性DNA聚合酶，并使其恶性转化鸡胚细胞的能力失活。INH-铜配合物与劳氏肉瘤病毒（RSV）的70S基因组RNA结合，这可能是其抑制RNA依赖性DNA聚合酶能力的原因。与同等结合两种核酸的M-IBT-铜配合物相比，该配合物与RNA的结合比与DNA的结合更有效。同聚物聚rA和聚rU比聚rC更易被INH-铜配合物结合。单独的异烟肼和单独的硫酸铜既不结合DNA、RNA、聚（rA）、聚（rU），也不结合聚（rC）。然而，单独的硫酸铜结合聚（rI）；单独的异烟肼则不结合。除了病毒DNA合成外，鸡胚细胞DNA合成也被INH-铜配合物抑制。细胞DNA合成的抑制程度大于细胞RNA和蛋白质合成的抑制程度。未观察到对先前感染劳氏肉瘤病毒的细胞转化有选择性抑制作用。
