Taechowisan Thongchai, Chuen-Im Thanaporn, Phutdhawong Waya S
Pak J Biol Sci. 2025 Apr;28(5):344-358. doi: 10.3923/pjbs.2025.344.358.
<b>Background and Objective:</b> Endophytic actinomycetes represent a promising source of novel bioactive compounds. This study aimed to isolate and characterize endophytic actinomycetes from <i>Aloe vera</i> leaves, identify their bioactive metabolites and assess their antimicrobial and anticancer properties. <b>Materials and Methods:</b> Endophytic actinomycetes were isolated from <i>Aloe vera</i> leaf sections and screened for antimicrobial activity. Isolate AVL08, exhibiting potent activity against <i>Staphylococcus aureus</i>, was identified using 16S rRNA gene sequencing and morphological characterization. Bioactive compounds were extracted, purified and identified using spectroscopic methods. Antimicrobial activity was evaluated using microbroth dilution assays and cytotoxicity was assessed against Vero, HeLa, HepG2 and MDA-MB-231 cell lines. Molecular docking studies were performed to investigate interactions with human DNA topoisomerase II. <i>In silico</i>, ADMET predictions were conducted using SwissADME, PreADMET and pkCSM. Statistical analysis was performed using SPSS (version 11.01) with One-way ANOVA and Tukey's <i>post hoc</i> test, considering differences significant at p<0.05. <b>Results:</b> Isolate AVL08 was identified as <i>Streptomyces galbus</i> and produced two anthraquinone compounds, 1,4,6-trihydroxy-8-(2'-oxopentyl)-9,10-anthraquinone (<b>1</b>) and 1,4,6-trihydroxy-8-pentacarboxyl-9,10-anthraquinone (<b>2</b>). These compounds exhibited selective antibacterial activity against Gram-positive bacteria and significant cytotoxicity against MDA-MB-231 and HeLa cancer cell lines, with IC<sub>50</sub> values ranging from 94.00 to 154.52 μg/mL. Compound <b>2</b> demonstrated enhanced potency and selectivity against HepG2 cells. Molecular docking revealed favorable interactions of the anthraquinones with topoisomerase II. The ADMET predictions indicated favorable pharmacokinetic profiles but highlighted potential hERG channel inhibition and mutagenicity in specific bacterial strains. <b>Conclusion:</b> <i>Streptomyces galbus</i> AVL08 is a promising source of bioactive anthraquinones with potent antimicrobial and anticancer properties. The identified compounds, particularly Compound <b>2</b>, warrant further investigation for therapeutic applications. This study highlights the potential of endophytic actinomycetes from <i>Aloe vera</i> as a valuable resource for drug discovery.
背景与目的：内生放线菌是新型生物活性化合物的一个有前景的来源。本研究旨在从库拉索芦荟叶片中分离并鉴定内生放线菌，确定其生物活性代谢产物，并评估其抗菌和抗癌特性。材料与方法：从库拉索芦荟叶片切片中分离内生放线菌，并筛选其抗菌活性。使用16S rRNA基因测序和形态学特征鉴定对金黄色葡萄球菌表现出强效活性的分离株AVL08。采用光谱法提取、纯化和鉴定生物活性化合物。使用微量肉汤稀释法评估抗菌活性，并针对Vero、HeLa、HepG2和MDA-MB-231细胞系评估细胞毒性。进行分子对接研究以研究与人类DNA拓扑异构酶II的相互作用。利用SwissADME、PreADMET和pkCSM进行计算机辅助的ADMET预测。使用SPSS（版本11.01）进行统计分析，采用单因素方差分析和Tukey事后检验，认为p<0.05时差异具有显著性。结果：分离株AVL08被鉴定为加尔维斯链霉菌，并产生了两种蒽醌化合物，1,4,6-三羟基-8-(2'-氧代戊基)-9,10-蒽醌（1）和1,4,6-三羟基-8-戊羧基-9,10-蒽醌（2）。这些化合物对革兰氏阳性菌表现出选择性抗菌活性，对MDA-MB-231和HeLa癌细胞系具有显著细胞毒性，IC50值范围为94.00至154.52 μg/mL。化合物2对HepG2细胞表现出增强的效力和选择性。分子对接显示蒽醌与拓扑异构酶II具有良好的相互作用。ADMET预测表明具有良好的药代动力学特征，但突出了潜在的hERG通道抑制和特定细菌菌株中的致突变性。结论：加尔维斯链霉菌AVL08是具有强效抗菌和抗癌特性的生物活性蒽醌的一个有前景的来源。所鉴定的化合物，特别是化合物2，值得进一步研究其治疗应用。本研究突出了库拉索芦荟内生放线菌作为药物发现的宝贵资源的潜力。
