The search for new therapies for the treatment of Arterial hypertension is a major concern in the scientific community. Here, we employ a computational biochemistry protocol to evaluate the performance of six compounds (Lig783, Lig1022, Lig1392, Lig2177, Lig3444 and Lig6199) to act as antihypertensive agents. This protocol consists of Docking experiments, efficiency calculations of ligands, molecular dynamics simulations, free energy, pharmacological and toxicological properties predictions (ADME-Tox) of the six ligands against Thermolysin. Our results show that the docked structures had an adequate orientation in the pocket of the Thermolysin enzymes, reproducing the X-ray crystal structure of Inhibitor-Thermolysin complexes in an acceptable way. The most promising candidates to act as antihypertensive agents among the series are Lig2177 and Lig3444. These compounds form the most stable ligand-Thermolysin complexes according to their binding free energy values obtained in the docking experiments as well as MM-GBSA decomposition analysis calculations. They present the lowest values of Ki, indicating that these ligands bind strongly to Thermolysin. Lig2177 was oriented in the pocket of Thermolysin in such a way that both OH of the dihydroxyl-amino groups to establish hydrogen bond interactions with Glu146 and Glu166. In the same way, Lig3444 interacts with Asp150, Glu143 and Tyr157. Additionally, Lig2177 and Lig3444 fulfill all the requirements established by Lipinski Veber and Pfizer 3/75 rules, indicating that these compounds could be safe compounds to be used as antihypertensive agents. We are confident that our computational biochemistry protocol can be used to evaluate and predict the behavior of a broad range of compounds designed in silicoagainst a protein target.

寻找用于治疗动脉高血压的新疗法是科学界的主要关注。在这里，我们采用了一种计算生物化学方法来评估六种化合物（Lig783，Lig1022，Lig1392，Lig2177，Lig3444和Lig6199）用作降压药的性能。该协议包括对接嗜热菌素的六个配体的对接实验，配体的效率计算，分子动力学模拟，自由能，药理和毒理学性质预测（ADME-Tox）。我们的结果表明，对接的结构在嗜热菌素酶的口袋中具有足够的取向，以可接受的方式复制了抑制剂-热溶素复合物的X射线晶体结构。该系列中最有希望成为抗高血压药的候选药物是Lig2177和Lig3444。根据在对接实验以及MM-GBSA分解分析计算中获得的结合自由能值，这些化合物形成最稳定的配体-热溶素复合物。它们呈现出最低的Ki值，表明这些配体与嗜热菌素强烈结合。将Lig2177定向在嗜热菌蛋白酶的口袋中，使二羟基-氨基的两个OH均与Glu146和Glu166建立氢键相互作用。同样，Lig3444与Asp150，Glu143和Tyr157相互作用。另外，Lig2177和Lig3444满足Lipinski Veber和Pfizer 3/75规则建立的所有要求，表明这些化合物可以用作抗高血压药的安全化合物。在计算机上针对蛋白质靶标。