Bisphosphonates constitute a group of pyrophosphate analogues therapeutically active against bone diseases. Numerous studies confirm their anticancer and antimetastatic potential as well as ability to relieve pathological pain. Although this is a known class of compounds, many aspects of their action remain unexplained and their new interaction partners are still being discovered. Due to the structural similarity to pyrophosphate, their interaction with pyrophosphate-recognizing enzymes seems to be feasible. In current work, the placental alkaline phosphatase (PLAP) is considered as a potential target for these class of compounds. PLAP is one of the enzymes responsible for degradation of pyrophosphate with high clinical significance. An elevation of PLAP level are considered as a potential cancer marker. An in silico study of complexes formed between selected phosphate derivatives and PLAP was performed. It indicates that all tested compounds: alendronic acid, clodronic acid, etidronic acid, zoledronic acid, imidodiphosphoric acid, pyrophosphoric acid, medronic acid, chloromethylenediphosphonic acid and hypophosphoric acid form a complexes with PLAP, stabilized by hydrogen bonds, hydrophobic and van der Waals interactions. Zoledronic acid, drug used in prevention of bone complications during cancer treatment was found to have the lowest estimated energy of binding (−6.6 kcal/mol). In silico study yielded very low energy of binding also for hypophosphate, equal −6.4 kcal/mol, despite having no identified hydrogen bonds. Subsequent molecular dynamic simulations, followed by molecular mechanics generalized-born surface area with pairwise decomposition calculations confirmed the stability of protein-ligand complexes. The results indicate that selected phosphate derivatives may potentially interact with the enzyme, changing its function, what should be investigated during in vitro studies.

双膦酸盐构成一组对骨疾病具有治疗活性的焦磷酸盐类似物。大量研究证实了它们的抗癌和抗转移潜力以及缓解病理性疼痛的能力。尽管这是一类已知的化合物，但其作用的许多方面仍未得到解释，其新的相互作用伙伴仍在被发现。由于与焦磷酸的结构相似，它们与焦磷酸识别酶的相互作用似乎是可行的。在目前的工作中，胎盘碱性磷酸酶 (PLAP) 被认为是这类化合物的潜在靶标。PLAP是负责降解焦磷酸的酶之一，具有很高的临床意义。PLAP 水平的升高被认为是潜在的癌症标志物。计算机_对选定的磷酸盐衍生物和 PLAP 之间形成的复合物进行了研究。这表明所有测试的化合物：阿仑膦酸、氯膦酸、依替膦酸、唑来膦酸、亚氨基二磷酸、焦磷酸、甲膦酸、氯亚甲基二膦酸和次磷酸与 PLAP 形成复合物，通过氢键、疏水和范德华相互作用稳定. 唑来膦酸是癌症治疗期间用于预防骨骼并发症的药物，被发现具有最低的估计结合能（-6.6 kcal/mol）。计算机尽管没有确定的氢键，但研究得出的连磷酸盐的结合能也非常低，等于 -6.4 kcal/mol。随后的分子动力学模拟，以及分子力学广义出生表面积和成对分解计算证实了蛋白质-配体复合物的稳定性。结果表明，选定的磷酸盐衍生物可能会与酶发生相互作用，从而改变其功能，这是体外研究中应研究的内容。