基于生物测定的方法从菊科蒿属植物（Artemisia afra）中分离和鉴定配子体杀灭化合物。
Bioassay-guided isolation and identification of gametocytocidal compounds from Artemisia afra (Asteraceae).
机构信息
Malaria Parasite Molecular Laboratory, Department of Biochemistry, Genetics and Microbiology, Faculty of Natural and Agricultural Sciences, Institute for Sustainable Malaria Control, University of Pretoria, Private Bag x20, Hatfield, 0028, South Africa.
Department of Chemistry, Faculty of Natural and Agricultural Sciences, Institute for Sustainable Malaria Control, University of Pretoria, Private Bag x20, Hatfield, 0028, South Africa.
出版信息
Malar J. 2019 Mar 8;18(1):65. doi: 10.1186/s12936-019-2694-1.
BACKGROUND
Optimal adoption of the malaria transmission-blocking strategy is currently limited by lack of safe and efficacious drugs. This has sparked the exploration of different sources of drugs in search of transmission-blocking agents. While plant species have been extensively investigated in search of malaria chemotherapeutic agents, comparatively less effort has been channelled towards exploring them in search of transmission-blocking drugs. Artemisia afra (Asteraceae), a prominent feature of South African folk medicine, is used for the treatment of a number of diseases, including malaria. In search of transmission-blocking compounds aimed against Plasmodium parasites, the current study endeavoured to isolate and identify gametocytocidal compounds from A. afra.
METHODS
A bioassay-guided isolation approach was adopted wherein a combination of solvent-solvent partitioning and gravity column chromatography was used. Collected fractions were continuously screened in vitro for their ability to inhibit the viability of primarily late-stage gametocytes of Plasmodium falciparum (NF54 strain), using a parasite lactate dehydrogenase assay. Chemical structures of isolated compounds were elucidated using UPLC-MS/MS and NMR data analysis.
RESULTS
Two guaianolide sesquiterpene lactones, 1α,4α-dihydroxybishopsolicepolide and yomogiartemin, were isolated and shown to be active (IC < 10 μg/ml; ~ 10 μM) against both gametocytes and intra-erythrocytic asexual P. falciparum parasites. Interestingly, 1α,4α-dihydroxybishopsolicepolide was significantly more potent against late-stage gametocytes than to early-stage gametocytes and intra-erythrocytic asexual P. falciparum parasites. Additionally, both isolated compounds were not overly cytotoxic against HepG2 cells in vitro.
CONCLUSION
This study provides the first instance of isolated compounds from A. afra against P. falciparum gametocytes as a starting point for further investigations on more plant species in search of transmission-blocking compounds.
背景
目前，由于缺乏安全有效的药物，疟疾传播阻断策略的最佳应用受到限制。这引发了人们对不同药物来源的探索，以期寻找传播阻断剂。虽然已经广泛研究了植物物种以寻找抗疟化学治疗药物，但在探索它们以寻找传播阻断药物方面的努力相对较少。南非民间医学中的一个重要特征——Afra（菊科），用于治疗多种疾病，包括疟疾。为了寻找针对疟原虫的传播阻断化合物，本研究旨在从 Afra 中分离和鉴定配子细胞杀伤化合物。
方法
采用生物测定指导的分离方法，采用溶剂-溶剂分配和重力柱色谱相结合的方法。收集的馏分在体外连续筛选，以评估其抑制恶性疟原虫（NF54 株）主要晚期配子体活力的能力，使用寄生虫乳酸脱氢酶测定法。使用 UPLC-MS/MS 和 NMR 数据分析来阐明分离化合物的化学结构。
结果
分离出两种愈创木烷倍半萜内酯，1α,4α-二羟基毕士朴醇内酯和艾草曲明，并证明它们对配子体和红内期无性恶性疟原虫寄生虫均具有活性（IC < 10 μg/ml；~10 μM）。有趣的是，1α,4α-二羟基毕士朴醇内酯对晚期配子体的活性明显高于早期配子体和红内期无性恶性疟原虫寄生虫。此外，两种分离的化合物在体外对 HepG2 细胞的细胞毒性均不高。
结论
本研究首次从 Afra 中分离出针对恶性疟原虫配子体的化合物，为进一步研究更多植物物种以寻找传播阻断化合物提供了起点。
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