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Abstract：
Tuberculosis is a highly lethal bacterial disease worldwide caused by Mycobacterium tuberculosis (Mtb). Caespitate is a phytochemical isolated from Helichrysum caespititium, 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 Mtb, specifically in the H37Rv strain: InhA, MabA, and UGM, enzymes involved in the formation of Mtb\'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 Mtb.
摘要：
结核病是全球范围内由结核分枝杆菌(Mtb)引起的高致死性细菌性疾病。Caespit酸盐是一种从菊苣中分离出的植物化学物质，一种用于非洲传统医学的植物，具有抗结核活性，但是它的作用方式仍然未知。建议在Mtb中有四个潜在的目标，特别是在H37Rv菌株中：InhA，马巴,和UGM,参与Mtb细胞壁形成的酶，还有PanK,在细胞生长中起作用。从气相（GC）和DMSO（CS）溶液中的DFT构象分析中选择了两种caespitate构象结构。分子对接计算,MM/GBSA分析，并进行了ADME参数评估。对接结果表明，当与PanK和UGM相互作用时，CS是首选的caespit构象。在这两种情况下，保留了caespitate分子结构的两个分子内氢键特征，从而获得了最稳定的配合物。MM/GBSA研究证实，PanK/caespitate和UGM/caespitate是最稳定的复合物。Caespit表现出良好的药代动力学特征，表明快速吸收，渗透性,和高生物利用度。此外,有人认为caespitate可能具有抗菌和抗菌活性。本研究为天然来源的抗结核药物的设计奠定了基础,特别是通过确定Mtb中潜在的药物靶标。
