A diverse range of 9-substituted 1,8-dioxohexahydroxanthenes was conceptualized and synthesized through a TFA-mediated approach in near quantitative yields without the use of column chromatography. From a series of 25 compounds, we found that compounds 14c and 14r exhibited promising anti-tuberculosis potential against avirulent and virulent strains of Mycobacterium tuberculosis with a Minimal Inhibitory Concentration (MIC) of 8 μg ml⁻¹, achieving 99% bactericidal activity at the same concentration. This series of compounds was found to be inactive against common Gram-positive and Gram-negative pathogens, indicating that the activity is mycobacteria-specific. Since the strategies for treating tuberculosis employ a combinatorial therapy, we tested and observed that the two lead compounds displayed synergistic behavior with known anti-TB drugs (ATDs) and a significant (16–32 fold) decrease in MIC values of both leads was observed in combination with either RIF or INH. Interestingly the lead molecule 14c displayed only time-dependent kill kinetics and sterilized the whole culture of Mycobacterium tuberculosis H37Rv in just 48 hours.

中文翻译：

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三氟乙酸介导的呫吨结构的合成及其广泛的抗结核评估

通过 TFA 介导的方法，在不使用柱色谱的情况下，以接近定量的产率概念化和合成了多种 9-取代 1,8-二氧六氢呫吨。从一系列 25 种化合物中，我们发现化合物14c和14r对结核分枝杆菌的无毒力和强毒株表现出良好的抗结核潜力，最低抑制浓度 (MIC) 为 8 μg ml ^-1，在相同的浓度。发现这一系列化合物对常见的革兰氏阳性和革兰氏阴性病原体没有活性，表明该活性是分枝杆菌特异性的。由于治疗结核病的策略采用组合疗法，我们测试并观察到这两种先导化合物与已知的抗结核药物 (ATD) 表现出协同行为，并且观察到两种先导化合物的 MIC 值显着降低（16-32 倍）与 RIF 或 INH 联合使用。有趣的是，先导分子14c仅表现出时间依赖性杀伤动力学，并在短短 48 小时内对结核分枝杆菌H37Rv 的整个培养物进行了灭菌。