Lee Hyun Woo, Choi Hansol, Nam Sang-Jip, Fenical William, Kim Hoon
Department of Pharmacy and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea.
Department of Chemistry and Nano Science, Ewha Womans University, Seoul 03760, Republic of Korea.
J Microbiol Biotechnol. 2017 Apr 28;27(4):785-790. doi: 10.4014/jmb.1612.12025.
Two piloquinone derivatives isolated from sp. CNQ-027 were tested for the inhibitory activities of two isoforms of monoamine oxidase (MAO), which catalyzes monoamine neurotransmitters. The piloquinone 4,7-dihydroxy-3-methyl-2-(4-methyl-1-oxopentyl)-6H-dibenzo[b,d]pyran-6-one (1) was found to be a highly potent inhibitor of human MAO-B, with an IC value of 1.21 µ; in addition, it was found to be highly effective against MAO-A, with an IC value of 6.47 µ. Compound 1 was selective, but not extremely so, for MAO-B compared with MAO-A, with a selectivity index value of 5.35. Compound 1,8-dihydroxy-2-methyl-3-(4-methyl-1-oxopentyl)-9,10-phenanthrenedione (2) was moderately effective for the inhibition of MAO-B (IC = 14.50 µ) but not for MAO-A (IC > 80 µ). There was no time-dependency in inhibition of MAO-A or -B by compound 1, and the MAO-A and -B activities were almost completely recovered in the dilution experiments with an excess amount of compound 1. Compound 1 showed competitive inhibition for MAO-A and -B, with values of 0.573 and 0.248 µ, respectively. These results suggest that piloquinones from a microbial source could be potent reversible MAO inhibitors and may be useful lead compounds for developing MAO enzyme inhibitors to treat related disorders, such as depression, Parkinson's disease, and Alzheimer's disease.
从 sp. CNQ-027 中分离出的两种对苯二醌衍生物，针对催化单胺神经递质的单胺氧化酶（MAO）的两种同工型的抑制活性进行了测试。对苯二醌 4,7 - 二羟基 - 3 - 甲基 - 2 - (4 - 甲基 - 1 - 氧代戊基) - 6H - 二苯并[b,d]吡喃 - 6 - 酮（1）被发现是一种高效的人源 MAO - B 抑制剂，IC 值为 1.21 μ；此外，还发现它对 MAO - A 也非常有效，IC 值为 6.47 μ。与 MAO - A 相比，化合物 1 对 MAO - B 具有选择性，但并非极其显著，选择性指数值为 5.35。化合物 1,8 - 二羟基 - 2 - 甲基 - 3 - (4 - 甲基 - 1 - 氧代戊基) - 9,10 - 菲醌（2）对 MAO - B 的抑制作用中等有效（IC = 14.50 μ），但对 MAO - A 无效（IC > 80 μ）。化合物 1 对 MAO - A 或 - B 的抑制不存在时间依赖性，并且在过量化合物 1 的稀释实验中，MAO - A 和 - B 的活性几乎完全恢复。化合物 1 对 MAO - A 和 - B 表现出竞争性抑制， 值分别为 0.573 和 0.248 μ。这些结果表明，来自微生物源的对苯二醌可能是有效的可逆 MAO 抑制剂，并且可能是开发用于治疗相关疾病（如抑郁症、帕金森病和阿尔茨海默病）的 MAO 酶抑制剂的有用先导化合物。
