合成了新型二氧联苯桥环三磷腈（DPP）三肽，并对其分子对接分析进行了研究，可视化了它们在各种癌细胞系受体内的结合特征以及体外细胞毒性和基因毒性特性。二肽化合物（Tyr-Phe）用各种氨基酸处理得到三肽化合物（Tyr-Phe-Gly、Tyr-Phe-Ala、Tyr-Phe-Val、Tyr-Phe-Phe、Tyr-Phe-Leu） ）。这些合成的三肽随后用DPP处理以获得具有三肽结构的新型磷腈化合物。本研究首次合成了以磷腈化合物为中心、侧臂为联苯和三肽基团的目标分子。对我们新合成的化合物进行体外细胞毒性研究，证明其对四种选定的人类癌细胞系具有抗癌特性，包括乳腺癌 (MCF-7)、卵巢 (A2780)、前列腺 (PC-3) 和结肠 (Caco-2)癌细胞。 Comet Assay分析确定大多数具有细胞毒活性的化合物的细胞死亡机制源于DNA损伤机制。在这些化合物中，DPP-Tyr-Phe-Phe 化合物似乎对受试细胞系（A2780 除外）具有最佳的抗癌活性，对乳腺癌、卵巢、前列腺的 IC50 值分别为 20.18、72.14、12.21 和 5.17 μM ，和结肠癌细胞系，分别。因此，对 DTPP 化合物进行了分子对接分析，以可视化其在与特定癌细胞系相关的靶酶结合位点内的结合几何形状和轮廓。分析表明，DTPP 衍生物在目标酶的结合位点内表现出最佳的结合构象和特征，与实验数据很好地吻合。根据数据，这些化合物被认为是药物和临床应用的强有力的候选分子。版权所有 © 2024 Elsevier Inc. 保留所有权利。

The novel dioxybiphenyl bridged-cyclotriphosphazenes (DPP) bearing tripeptide were synthesized and investigated for their molecular docking analysis, visualizing their binding profiles within various cancer cell line receptors and in vitro cytotoxic and genotoxic properties. The dipeptide compound (Tyr-Phe) was treated with various amino acids to obtain the tripeptide compounds (Tyr-Phe-Gly, Tyr-Phe-Ala, Tyr-Phe-Val, Tyr-Phe-Phe, and Tyr-Phe-Leu). These synthesized tripeptides were subsequently treated with DPP to obtain novel phosphazene compounds bearing tripeptide structures. As a result, the synthesis of target molecules with phosphazene compound in the center and biphenyl and tripeptide groups in the side arms was obtained for the first time in this study. Examining the cytotoxic studies in vitro of our newly synthesized compounds demonstrated the anticancer properties against four selected human cancer cell lines, including breast (MCF-7), ovarian (A2780), prostate (PC-3), and colon (Caco-2) cancer cells. The Comet Assay analysis determined that the cell death mechanism of most of the compounds with cytotoxic activity stemmed from the DNA damage mechanism. Among the compounds, the DPP-Tyr-Phe-Phe compound seems to have the best anticancer activity against the subjected cell lines (Except for A2780) with IC50 values equal to 20.18, 72.14, 12.21, and 5.17 μM against breast, ovarian, prostate, and colon cancer cell lines, respectively. For this reason, the molecular docking analysis was conducted for the DTPP compound to visualize its binding geometry and profile within the target enzyme's binding site associated with the specific cancer cell line. The analysis revealed that the DTPP derivative exhibited an optimal binding conformation and characteristics within the target enzyme's binding site, aligning well with the experimental data. Based on the data, these compounds are believed to be strong candidate molecules for both pharmaceutical and clinical applications.Copyright © 2024 Elsevier Inc. All rights reserved.