Inhibition of Bordetella pertussis adenylate cyclase toxin (ACT) and Bacillus anthracis edema factor (EF), key virulence factors with adenylate cyclase activity, represents a potential method for treating or preventing toxemia related to whooping cough and anthrax, respectively. Novel α‐branched acyclic nucleoside phosphonates (ANPs) having a hemiaminal ether moiety were synthesized as potential inhibitors of bacterial adenylate cyclases. ANPs prepared as bisamidates were not cytotoxic, but did not exhibit any profound activity (IC₅₀>10 μm) toward ACT in J774A.1 macrophages. The apparent lack of activity of the bisamidates is speculated to be due to the inefficient formation of the biologically active species (ANPpp) in the cells. Conversely, two 5‐haloanthraniloyl‐substituted ANPs in the form of diphosphates were shown to be potent ACT and EF inhibitors with IC₅₀ values ranging from 55 to 362 nm.

中文翻译：

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α-支链无环核苷膦酸酯的合成作为细菌腺苷酸环化酶的潜在抑制剂

抑制百日咳博德特氏菌腺苷酸环化酶毒素（ACT）和具有腺苷酸环化酶活性的关键毒力因子炭疽杆菌水肿因子（EF），代表了一种潜在的治疗或预防与百日咳和炭疽有关的毒血症的方法。合成具有半胱氨酸醚部分的新型α分支无环核苷膦酸酯（ANP）作为细菌腺苷酸环化酶的潜在抑制剂。制备为双氨基甲酸酯的ANP没有细胞毒性，但没有表现出任何深远的活性（IC ₅₀ > 10μm）朝着J774A.1巨噬细胞中的ACT迈进。据推测，双氨基甲酸酯活性的明显缺乏是由于细胞中生物活性物质（ANPpp）形成效率低下所致。相反，显示出两种以二磷酸盐形式被5-卤代蒽基取代的ANPs是有效的ACT和EF抑制剂，IC ₅₀值在55至362 n m之间。