Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia.
Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia.
Braz J Med Biol Res. 2023 Apr 7;56:e12404. doi: 10.1590/1414-431X2023e12404. eCollection 2023.
Secondary metabolites produced by endophytes are an excellent source of biologically active compounds. The newly isolated natural products terezine E and 14-hydroxyterezine D are endophytic metabolites exhibiting anticancer activity recently identified by our team (https://doi.org/10.1080/14786419.2018.1489393). In our current study, we evaluated their affinity for binding to the active site of histone deacetylase (PDB ID: 4CBT) and matrix metalloproteinase 9 (PDB ID: 4H3X) by molecular docking using AutoDock Vina software after having tested their cytotoxic activities on three cell lines (human ductal breast epithelial tumor cells (T47D)-HCC1937), human hepatocarcinoma cell line (HepG2)-HB8065), and human colorectal carcinoma cells (HCT-116)-TCP1006, purchased from ATCC, USA)). Additionally, their antimicrobial activities were investigated, and their minimum inhibitory concentration (MIC) values were determined against P. notatum and S. aureus by the broth microdilution method. Higher cytotoxicity was observed for terezine E against all tested cell lines compared to 14-hydroxyterezine D. Molecular docking results supported the high cytotoxicity of terezine E and showed higher binding affinity with 4CBT with an energy score of 9 kcal/mol. Terezine E showed higher antibacterial and antifungal activities than 14-hydroxyrerezine D: MIC values were 15.45 and 21.73 µg/mL against S. aureus and 8.61 and 11.54 µg/mL against P. notatum, respectively.
内生真菌产生的次生代谢产物是生物活性化合物的极好来源。我们的团队最近新分离出的天然产物特雷齐因 E 和 14-羟基特雷齐因 D 是具有抗癌活性的内生代谢产物（https://doi.org/10.1080/14786419.2018.1489393）。在我们目前的研究中，我们使用 AutoDock Vina 软件通过分子对接评估了它们与组蛋白去乙酰化酶（PDB ID：4CBT）和基质金属蛋白酶 9（PDB ID：4H3X）的活性位点结合的亲和力，此前我们已经在三种细胞系（人乳腺导管上皮肿瘤细胞（T47D-HCC1937）、人肝癌细胞系（HepG2-HB8065）和人结肠直肠癌细胞系（HCT-116-TCP1006）上测试了它们的细胞毒性。这些细胞系均购自美国 ATCC）。此外，还研究了它们的抗菌活性，并通过肉汤微量稀释法测定了它们对 P. notatum 和 S. aureus 的最小抑菌浓度（MIC）值。与 14-羟基特雷齐因 D 相比，特雷齐因 E 对所有测试的细胞系表现出更高的细胞毒性。分子对接结果支持特雷齐因 E 的高细胞毒性，并显示与 4CBT 具有更高的结合亲和力，能量评分为 9 kcal/mol。特雷齐因 E 表现出比 14-羟基特雷齐因 D 更高的抗菌和抗真菌活性：对 S. aureus 的 MIC 值分别为 15.45 和 21.73 µg/mL，对 P. notatum 的 MIC 值分别为 8.61 和 11.54 µg/mL。
