Fu Chunqing, Shi Henan, Chen Hong, Zhang Keyu, Wang Manyuan, Qiu Feng
Beijing Key Laboratory of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China.
ACS Omega. 2020 Dec 28;6(1):889-899. doi: 10.1021/acsomega.0c05465. eCollection 2021 Jan 12.
Deoxyartemisinin, a compound separated from L., shows anti-inflammatory and antiulcer activities. 10-Deoxoartemisinin is a novel compound with a strong antimalarial effect derivatized from artemisinin. Compared to the famous antimalarial natural compound artemisinin, deoxyartemisinin lacks the peroxide bridge structure, while 10-deoxoartemisinin remains this special peroxide bridge group but loses the 10-position keto group. To clarify their pharmacological differences, the absorption, distribution, metabolism, excretion (ADME) properties of artemisinin, deoxyartemisinin, and 10-deoxoartemisinin were first predicted using QikProp software. Also, their pharmacokinetic behaviors in rats were further evaluated by a rapid, sensitive, and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method after oral and intravenous administration of each compound, in which deoxyartemisinin and 10-deoxoartemisinin were first evaluated for their pharmacokinetics. All parameters about ADME properties calculated by software met the criteria and the ADME performance order was 10-deoxoartemisinin > deoxyartemisinin > artemisinin. The oral bioavailability of artemisinin was calculated to be 12.2 ± 0.832%, which was about 7 times higher than that of deoxyartemisinin (1.60 ± 0.317%). For 10-deoxoartemisinin, its bioavailability (26.1 ± 7.04%) was superior to artemisinin at a degree of more than twice. Considering their chemical structures, losing the peroxide bridge might decrease the absorption rate of deoxyartemisinin in the gastrointestinal tract, while retaining the peroxide bridge but losing the 10-position ketone might improve the bioavailability of 10-deoxoartemisinin.
从青蒿中分离出的化合物脱氧青蒿素具有抗炎和抗溃疡活性。10-脱氧青蒿素是一种从青蒿素衍生而来的具有强抗疟作用的新型化合物。与著名的抗疟天然化合物青蒿素相比，脱氧青蒿素缺乏过氧化物桥结构，而10-脱氧青蒿素保留了这个特殊的过氧化物桥基团，但失去了10位酮基。为阐明它们的药理差异，首先使用QikProp软件预测青蒿素、脱氧青蒿素和10-脱氧青蒿素的吸收、分布、代谢、排泄（ADME）特性。此外，在口服和静脉注射每种化合物后，通过快速、灵敏且特异的液相色谱-串联质谱（LC-MS/MS）方法进一步评估它们在大鼠体内的药代动力学行为，其中首次对脱氧青蒿素和10-脱氧青蒿素的药代动力学进行了评估。软件计算得出的所有ADME特性参数均符合标准，ADME性能顺序为10-脱氧青蒿素>脱氧青蒿素>青蒿素。计算得出青蒿素的口服生物利用度为12.2±0.832%，约为脱氧青蒿素（1.60±0.317%）的7倍。对于10-脱氧青蒿素，其生物利用度（26.1±7.04%）比青蒿素高出一倍多。考虑到它们的化学结构，失去过氧化物桥可能会降低脱氧青蒿素在胃肠道的吸收速率，而保留过氧化物桥但失去10位酮基可能会提高10-脱氧青蒿素的生物利用度。
