In this study, the molecular descriptors (MDs) of a set of halogenated benzooxazepines (BZOs) were evaluated to determine their absorption, distribution, metabolism, excretion, and toxicity properties. Molecular docking and dynamics analyses were performed to investigate the action mechanisms. The optimization of BZOs was carried out using density function theory with Becke’s three parameter hybrid functional (B3LYP) at the 6-31G+(d,p) level. Which was further correlated with theoretical and experimental spectroscopic values. Detailed studies were performed on frontier molecular orbitals, quantum chemical descriptors, IR, and NMR spectroscopy. A preliminary structure–activity relationship analysis revealed that BZOs bearing Cl substitution had greater effectiveness, particularly when positioned at the R-position on the BZO-e system. Further BZOs were used as inhibitors of apoptosis pathway-related protein targets, including caspase 8, caspase 3, Bcl-2, Bcl-xl, BAD, BAX, apoptotic protease-activating factor 1, poly [ADP-ribose] polymerase 1 (PARP1), and tankyrase 1 for potential anticancer activity. The stability of the receptor-inhibitor complex was validated by the molecular dynamics analysis of the PARP1 complex.

中文翻译：

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使用多管齐下的计算和结构方法测定苯并恶氮卓 (BZO) 衍生物的抗癌活性和作用机制

在这项研究中，评估了一组卤代苯并氧氮杂卓 (BZO) 的分子描述符 (MD)，以确定它们的吸收、分布、代谢、排泄和毒性特性。进行分子对接和动力学分析以研究作用机制。 BZO 的优化是使用密度函数理论和 Becke 的三参数混合泛函 (B3LYP) 在 6-31G+(d,p) 水平上进行的。这进一步与理论和实验光谱值相关。对前沿分子轨道、量子化学描述符、红外和核磁共振光谱进行了详细研究。初步构效关系分析表明，具有 Cl 取代基的 BZO 具有更高的有效性，特别是当位于 BZO-e 系统的 R 位时。此外，BZO 还被用作凋亡途径相关蛋白靶标的抑制剂，包括 caspase 8、caspase 3、Bcl-2、Bcl-xl、BAD、BAX、凋亡蛋白酶激活因子 1、聚 [ADP-核糖] 聚合酶 1 (PARP1) ) 和端锚聚合酶 1 具有潜在的抗癌活性。通过 PARP1 复合物的分子动力学分析验证了受体-抑制剂复合物的稳定性。