Moreno-Ceballos Andrea, Caballero Norma A, Castro María Eugenia, Perez-Aguilar Jose Manuel, Mammino Liliana, Melendez Francisco J
Laboratorio de Química Teórica, Centro de Investigación, Departamento de Fisicoquímica, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Edif. FCQ10, 22 Sur y San Claudio, Ciudad Universitaria, Col. San Manuel, Puebla C.P. 72570, Mexico.
Facultad de Ciencias Biológicas, Benemérita Universidad Autónoma de Puebla, Edif. BIO1, 22 Sur y San Claudio, Ciudad Universitaria, Col. San Manuel, Puebla C.P. 72570, Mexico.
Curr Issues Mol Biol. 2024 Jun 27;46(7):6489-6507. doi: 10.3390/cimb46070387.
Tuberculosis is a highly lethal bacterial disease worldwide caused by (). Caespitate is a phytochemical isolated from , a plant used in African traditional medicine that shows anti-tubercular activity, but its mode of action remains unknown. It is suggested that there are four potential targets in , specifically in the H37Rv strain: InhA, MabA, and UGM, enzymes involved in the formation of 's cell wall, and PanK, which plays a role in cell growth. Two caespitate conformational structures from DFT conformational analysis in the gas phase (GC) and in solution with DMSO (CS) were selected. Molecular docking calculations, MM/GBSA analysis, and ADME parameter evaluations were performed. The docking results suggest that CS is the preferred caespitate conformation when interacting with PanK and UGM. In both cases, the two intramolecular hydrogen bonds characteristic of caespitate's molecular structure were maintained to achieve the most stable complexes. The MM/GBSA study confirmed that PanK/caespitate and UGM/caespitate were the most stable complexes. Caespitate showed favorable pharmacokinetic characteristics, suggesting rapid absorption, permeability, and high bioavailability. Additionally, it is proposed that caespitate may exhibit antibacterial and antimonial activity. This research lays the foundation for the design of anti-tuberculosis drugs from natural sources, especially by identifying potential drug targets in .
结核病是一种由（）引起的全球范围内极具致死性的细菌性疾病。凯斯皮泰是从一种用于非洲传统医学的植物中分离出的一种植物化学物质，它具有抗结核活性，但其作用方式尚不清楚。研究表明，在（此处原文缺失具体内容）中，特别是在H37Rv菌株中有四个潜在靶点：参与（此处原文缺失具体内容）细胞壁形成的InhA、MabA和UGM酶，以及在细胞生长中起作用的PanK。从气相（GC）和二甲基亚砜（DMSO）溶液（CS）中的密度泛函理论（DFT）构象分析中选择了两种凯斯皮泰构象结构。进行了分子对接计算、MM/GBSA分析和ADME参数评估。对接结果表明，与PanK和UGM相互作用时，CS是凯斯皮泰的首选构象。在这两种情况下，凯斯皮泰分子结构特有的两个分子内氢键得以维持，以形成最稳定的复合物。MM/GBSA研究证实，PanK/凯斯皮泰复合物和UGM/凯斯皮泰复合物是最稳定的。凯斯皮泰显示出良好的药代动力学特征，表明其吸收快、渗透性好且生物利用度高。此外，有人提出凯斯皮泰可能具有抗菌和抗锑活性。这项研究为从天然来源设计抗结核药物奠定了基础，特别是通过确定（此处原文缺失具体内容）中的潜在药物靶点。
