In Vivo Efficacy and Metabolism of the Antimalarial Cycleanine and Improved In Vitro Antiplasmodial Activity of Semisynthetic Analogues
文献类型：期刊论文
| 作者 | Uche, Fidelia Ijeoma2; Guo, Xiaozhen3; Okokon, Jude4; Ullah, Imran1; Horrocks, Paul1; Boateng, Joshua5; Huang, Chenggang3 ; Li, Wen-Wu2
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| 刊名 | ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
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| 出版日期 | 2021-02-01 |
| 卷号 | 65期号:2页码:11 |
| 关键词 | malaria Plasmodium falciparum Plasmodium berghei bisbenzylisoquinoline alkaloids cycleanine metabolism in vivo activity antimalarial agents drug metabolism |
| ISSN号 | 0066-4804 |
| DOI | 10.1128/AAC.01995-20 |
| 通讯作者 | Huang, Chenggang(cghuang@simm.ac.cn) ; Li, Wen-Wu(w.li@keele.ac.uk) |
| 英文摘要 | Bisbenzylisoquinoline (BBIQ) alkaloids are a diverse group of natural products that demonstrate a range of biological activities. In this study, the in vitro antiplasmodial activity of three BBIQ alkaloids (cycleanine [compound 1], isochondodendrine [compound 2], and 29-norcocsuline [compound 3]) isolated from the Triclisia subcordata Oliv. medicinal plant traditionally used for the treatment of malaria in Nigeria are studied alongside two semisynthetic analogues (compounds 4 and 5) of cycleanine. The antiproliferative effects against a chloroquine-resistant Plasmodium falciparum strain were determined using a SYBR green 1 fluorescence assay. The in vivo antimalarial activity of cycleanine is then investigated in suppressive, prophylactic, and curative murine malaria models after infection with a chloroquine-sensitive Plasmodium berghei strain. BBIQ alkaloids (compounds 1 to 5) exerted in vitro antiplasmodial activities with 50% inhibitory concentration (IC50) at low micromolar concentrations and the two semisynthetic cycleanine analogues showed an improved potency and selectivity compared to those of cycleanine. At oral doses of 25 and 50mg/kg body weight of infected mice, cycleanine suppressed the levels of parasitemia and increased mean survival times significantly compared to those of the control groups. The metabolites and metabolic pathways of cycleanine were also studied using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Twelve novel metabolites were detected in rats after intragastric administration of cycleanine. The metabolic pathways of cycleanine were demonstrated to involve hydroxylation, dehydrogenation, and demethylation. Overall, these in vitro and in vivo results provide a basis for the future evaluation of cycleanine and its analogues as leads for further development. |
| WOS关键词 | BISBENZYLISOQUINOLINE ALKALOIDS ; PLASMODIUM-FALCIPARUM ; ROOT-BARK ; STEM-BARK ; CYTOTOXICITY ; FRACTIONS ; APOPTOSIS ; MALARIA |
| 资助项目 | Nigerian ETF ; NDDC ; BBSRC |
| WOS研究方向 | Microbiology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000609954100037 |
| 出版者 | AMER SOC MICROBIOLOGY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/295922]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Huang, Chenggang; Li, Wen-Wu |
| 作者单位 | 1.Keele Univ, Sch Med, Stoke On Trent, Staffs, England 2.Keele Univ, Sch Pharm & Bioengn, Stoke On Trent, Staffs, England 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 4.Univ Uyo, Fac Pharm, Dept Pharmacol & Toxicol, Uyo, Nigeria 5.Univ Greenwich, Sch Sci, London, England |
| 推荐引用方式 GB/T 7714 | Uche, Fidelia Ijeoma,Guo, Xiaozhen,Okokon, Jude,et al. In Vivo Efficacy and Metabolism of the Antimalarial Cycleanine and Improved In Vitro Antiplasmodial Activity of Semisynthetic Analogues[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,2021,65(2):11. |
| APA | Uche, Fidelia Ijeoma.,Guo, Xiaozhen.,Okokon, Jude.,Ullah, Imran.,Horrocks, Paul.,...&Li, Wen-Wu.(2021).In Vivo Efficacy and Metabolism of the Antimalarial Cycleanine and Improved In Vitro Antiplasmodial Activity of Semisynthetic Analogues.ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,65(2),11. |
| MLA | Uche, Fidelia Ijeoma,et al."In Vivo Efficacy and Metabolism of the Antimalarial Cycleanine and Improved In Vitro Antiplasmodial Activity of Semisynthetic Analogues".ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 65.2(2021):11. |
入库方式： OAI收割
来源：上海药物研究所
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