National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA.
Natural Products Utilization Research Unit, Agricultural Research Service, U.S. Department of Agriculture, University of Mississippi, Oxford, MS 38677, USA.
Molecules. 2020 Dec 18;25(24):6000. doi: 10.3390/molecules25246000.
Two new epimeric bibenzylated monoterpenes machaerifurogerol () and 5--machaerifurogerol (), and four known isoflavonoids (+)-vestitol (), 7--methylvestitol (), (+)-medicarpin (), and 3,8-dihydroxy-9-methoxypterocarpan () were isolated from Pers. This plant was previously assigned as Spruce, from which machaeriols A-D (-) and machaeridiols A-C (-) were reported, and all were then re-isolated, except the minor compound , for a comprehensive antimicrobial activity evaluation. Structures of the isolated compounds were determined by full NMR and mass spectroscopic data. Among the isolated compounds, the mixture + was the most active with an MIC value of 1.25 μg/mL against methicillin-resistant (MRSA) strains BAA 1696, -1708, -1717, -33591, and vancomycin-resistant (VRE 700221) and . (VRE 51299) and vancomycin-sensitive (VSE 29212). Compounds - and - were found to be more potent against MRSA 1708, and , , and against VRE 700221, than the drug control ciprofloxacin and vancomycin. A combination study using an in vitro Checkerboard method was carried out for machaeriols ( or ) and machaeridiols ( or ), which exhibited a strong synergistic activity of + (MIC 0.156 and 0.625 µg/mL), with >32- and >8-fold reduction of MIC's, compared to , against MRSA 1708 and -1717, respectively. In the presence of sub-inhibitory concentrations on polymyxin B nonapeptide (PMBN), compounds + , , , and showed activity in the range of 0.5-8 µg/mL for two strains of , 2-16 µg/mL against PAO1, and 2 µg/mL against NCTC 12923, but were inactive (MIC > 64 µg/mL) against the two isolates of .
从 Pers. 中分离得到两种新的差向异构双苄基单萜 machaerifurogerol () 和 5--machaerifurogerol (), 四种已知的异黄酮 (+)-vestitol (), 7--methylvestitol (), (+)-medicarpin () 和 3,8-二羟基-9-甲氧基紫檀烷 ()。该植物以前被分配为 Spruce，从中分离出了 machaeriols A-D (-) 和 machaeridiols A-C (-)，除了微量化合物 外，所有化合物都被重新分离出来，以进行全面的抗菌活性评价。通过全 NMR 和质谱数据确定了分离化合物的结构。在所分离的化合物中，混合物 + 对耐甲氧西林金黄色葡萄球菌 (MRSA) 菌株 BAA 1696、-1708、-1717、-33591 和万古霉素耐药金黄色葡萄球菌 (VRE 700221) 和 最有效，MIC 值为 1.25 μg/mL。化合物 - 和 - 对 MRSA 1708 更为有效，对 VRE 700221 更为有效，对 则更有效，而药物对照环丙沙星和万古霉素则更有效。采用体外棋盘法对 machaeriols ( 或 ) 和 machaeridiols ( 或 ) 进行了联合研究，结果表明 + 具有很强的协同作用 (MIC 0.156 和 0.625 µg/mL)，与 相比，MRSA 1708 和 -1717 的 MIC 值降低了 32 倍和 8 倍以上。在亚抑菌浓度下，化合物 +,,, 和 对多粘菌素 B 九肽 (PMBN) 表现出活性，两种 菌株的活性范围为 0.5-8 µg/mL，对 PAO1 的活性范围为 2-16 µg/mL，对 NCTC 12923 的活性范围为 2 µg/mL，但对两种 分离株无效 (MIC > 64 µg/mL)。
