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Abstract：
BACKGROUND: The erythrocytic stage of the life cycle of the malaria parasite, Plasmodium falciparum, consists of trophozoite, schizont and gametocyte stages in humans. Various anti-malarial agents target different stages of the parasite to produce treatment outcomes. This study reports on the stage-specific anti-malarial activity of heptaphylline and imperatorin against human P. falciparum in addition to their cytotoxicity and selectivity indices (SI).
METHODS: The compounds were isolated from Clausena anisata using column chromatography and their structures elucidated using NMR spectroscopy. The anti-malarial activity was determined by measuring the trophozoitocidal, schizonticidal and gametocytocidal activities of the compounds using the SYBR green assay. Cytotoxicity was evaluated using the tetrazolium-based colorimetric assay.
RESULTS: Heptaphylline and imperatorin produced trophozoitocidal, schizonticidal and gametocytocidal activities with IC50s of 1.57 (0.2317)-26.92 (0.3144) µM with those of artesunate (the standard drug) being 0.00024 (0.0036)-0.0070 (0.0013) µM. In the cytotoxicity assay, the compounds produced CC50S greater than 350 µM and SI of 13.76-235.90. Also, the trophozoitocidal and schizonticidal activities of the compounds were more pronounced than their gametocytocidal activity. Imperatorin was 42.04% more trophozoitocidal than hepthaphyline. However, hepthaphyline has more schizonticidal and gametocytocidal properties than imperatorin.
CONCLUSIONS: Heptaphylline and imperatorin are promising anti-malarial agents, since they possess potent anti-malarial activity with weak cytotoxicity on RBCs. However, imperatorin is a better anti-malarial prophylactic agent whereas heptaphylline is a better malaria treatment agent.
METHODS: The compounds were isolated from Clausena anisata using column chromatography and their structures elucidated using NMR spectroscopy. The anti-malarial activity was determined by measuring the trophozoitocidal, schizonticidal and gametocytocidal activities of the compounds using the SYBR green assay. Cytotoxicity was evaluated using the tetrazolium-based colorimetric assay.
RESULTS: Heptaphylline and imperatorin produced trophozoitocidal, schizonticidal and gametocytocidal activities with IC50s of 1.57 (0.2317)-26.92 (0.3144) µM with those of artesunate (the standard drug) being 0.00024 (0.0036)-0.0070 (0.0013) µM. In the cytotoxicity assay, the compounds produced CC50S greater than 350 µM and SI of 13.76-235.90. Also, the trophozoitocidal and schizonticidal activities of the compounds were more pronounced than their gametocytocidal activity. Imperatorin was 42.04% more trophozoitocidal than hepthaphyline. However, hepthaphyline has more schizonticidal and gametocytocidal properties than imperatorin.
CONCLUSIONS: Heptaphylline and imperatorin are promising anti-malarial agents, since they possess potent anti-malarial activity with weak cytotoxicity on RBCs. However, imperatorin is a better anti-malarial prophylactic agent whereas heptaphylline is a better malaria treatment agent.
摘要：
背景：疟疾寄生虫生命周期的红细胞阶段，恶性疟原虫,由滋养体组成，人类的分裂和配子体阶段。各种抗疟疾剂靶向寄生虫的不同阶段以产生治疗结果。这项研究报道了七茶碱和欧前胡素对人恶性疟原虫的阶段特异性抗疟疾活性，以及它们的细胞毒性和选择性指数（SI）。
方法：使用柱色谱法从Clausenaanisata中分离化合物，并使用NMR光谱阐明其结构。抗疟疾活性是通过测量的滋养杀动物，使用SYBR绿色测定法对化合物的杀分裂和杀配子细胞活性。使用基于四唑的比色测定法评估细胞毒性。
结果：七叶树素和欧前胡素产生了滋养杀动物，杀生和杀配子细胞活性，IC50为1.57（0.2317）-26.92（0.3144）µM，青蒿琥酯（标准药物）的IC50为0.00024（0.0036）-0.0070（0.0013）µM。在细胞毒性试验中,化合物产生的CC50S大于350µM，SI为13.76-235.90。此外，化合物的杀虫和杀裂殖子活性比其杀配子细胞活性更明显。Imperatorin比hepthaphenline高出42.04％。然而,hepthaphine比欧前胡素具有更多的杀分裂子和杀配子细胞特性。
结论：七肽和欧前胡素是有前途的抗疟疾药，因为它们具有有效的抗疟疾活性，对红细胞具有弱的细胞毒性。然而,欧前胡素是一种更好的抗疟疾预防剂，而七茶碱是一种更好的疟疾治疗剂。
方法：使用柱色谱法从Clausenaanisata中分离化合物，并使用NMR光谱阐明其结构。抗疟疾活性是通过测量的滋养杀动物，使用SYBR绿色测定法对化合物的杀分裂和杀配子细胞活性。使用基于四唑的比色测定法评估细胞毒性。
结果：七叶树素和欧前胡素产生了滋养杀动物，杀生和杀配子细胞活性，IC50为1.57（0.2317）-26.92（0.3144）µM，青蒿琥酯（标准药物）的IC50为0.00024（0.0036）-0.0070（0.0013）µM。在细胞毒性试验中,化合物产生的CC50S大于350µM，SI为13.76-235.90。此外，化合物的杀虫和杀裂殖子活性比其杀配子细胞活性更明显。Imperatorin比hepthaphenline高出42.04％。然而,hepthaphine比欧前胡素具有更多的杀分裂子和杀配子细胞特性。
结论：七肽和欧前胡素是有前途的抗疟疾药，因为它们具有有效的抗疟疾活性，对红细胞具有弱的细胞毒性。然而,欧前胡素是一种更好的抗疟疾预防剂，而七茶碱是一种更好的疟疾治疗剂。
