Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Molecules. 2019 Oct 28;24(21):3874. doi: 10.3390/molecules24213874.
10-deoxoartemisinin is a semisynthetic derivative of artemisinin that lacks a lactone carbonyl group at the 10-position, and has stronger antimalarial properties than artemisinin. However, 10-deoxoartemisinin has limited utility as a therapeutic agent because of its low solubility and bioavailability. Hydroxylated 10-deoxoartemisinins are a series of properties-improved derivatives. Via microbial transformation, which can hydroxylate 10-deoxoartemisinin at multiple sites, the biotransformation products of 10-deoxoartemisinin have been investigated in this paper. Using ultra-performance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS) combined with UNIFI software, products of microbial transformation of 10-deoxoartemisinin were rapidly and directly analyzed. The hydroxylation abilities of nine microorganisms were compared using this method. All of the microorganisms evaluated were able to hydroxylate 10-deoxoartemisinin, and a total of 35 hydroxylated products were identified. These can be grouped into dihydroxylated 10-deoxoartemisinins, monohydroxylated 10-deoxoartemisinins, hydroxylated dehydrogenated 10-deoxoartemisinins, and hydroxylated hydrogenated 10-deoxoartemisinins. and are able to hydroxylate 10-deoxoartemisinin, and their biotransformation products are investigated here for the first time. CICC 40250 was shown to most efficiently hydroxylate 10-deoxoartemisinin, and could serve as a model organism for microbial transformation. This method could be used to generate additional hydroxylated 10-deoxoartemisinins for further research.
10-去氧青蒿素是青蒿素的半合成衍生物，其 10 位缺少内酯羰基，比青蒿素具有更强的抗疟作用。然而，由于其溶解度和生物利用度低，10-去氧青蒿素作为治疗剂的用途有限。羟基化 10-去氧青蒿素是一系列性质改善的衍生物。通过微生物转化，可以在多个位点羟基化 10-去氧青蒿素，本文研究了 10-去氧青蒿素的生物转化产物。采用超高效液相色谱-电喷雾电离-四极杆飞行时间质谱联用（UPLC-ESI-Q-TOF-MS）结合 UNIFI 软件，快速直接分析 10-去氧青蒿素微生物转化的产物。该方法比较了九种微生物的羟化能力。评价的所有微生物都能够羟基化 10-去氧青蒿素，共鉴定出 35 种羟基化产物。这些可以分为二羟基化 10-去氧青蒿素、单羟基化 10-去氧青蒿素、羟基化脱氢 10-去氧青蒿素和羟基化氢化 10-去氧青蒿素。和能够羟基化 10-去氧青蒿素，其生物转化产物在这里首次进行了研究。CICC 40250 被证明能够最有效地羟基化 10-去氧青蒿素，可作为微生物转化的模式生物。该方法可用于生成更多的羟基化 10-去氧青蒿素，用于进一步研究。
