Antiplasmodial Compounds from Deep-Water Marine Invertebrates.
Antiplasmodial Compounds from Deep-Water Marine Invertebrates.
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来自深水海洋无脊椎动物的抗疟原虫化合物。
DOI：
10.3390/md19040179
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发表时间：
2021-03-25
期刊：
影响因子：
5.4
通讯作者：
Chakrabarti D
中科院分区：
文献类型：
--
作者：
Wright AE;Collins JE;Roberts B;Roberts JC;Winder PL;Reed JK;Diaz MC;Pomponi SA;Chakrabarti D
由于对所有现有药物的耐药性普遍出现，迫切需要用于疟疾治疗的新药先导。针对恶性疟原虫氯喹抗性菌株（Dd 2）筛选Harbor分支富集级分文库，随后通过生物测定引导的分级分离，导致鉴定出两种有效的抗疟原虫剂;命名为贝布霉素A的新型二萜（1）和已知的C21降解的萜类尼替宁（2）。采用SYBR绿色I试验确定贝布霉素A和尼替宁的Dd 2 EC 50分别为1.08 ± 0.21和0.29 ± 0.02 µM。然后进行进一步分析，以评估抑制剂抗疟原虫作用对Dd 2红细胞内生命周期的阶段特异性。发现如果在侵入后42小时的晚期雌配子体形成之前的任何时间加入，暴露于贝布霉素A会阻断寄生虫在雌配子体阶段的成熟（HPI）。相比之下，早期生命周期暴露于镍蛋白（18 HPI之前）被确定为对寄生虫抑制至关重要，这表明镍蛋白可能在从环到早期滋养体（6-18 HPI）的过渡期间靶向寄生虫的成熟，这是已知抗疟药物中的一种新特性。
Novel drug leads for malaria therapy are urgently needed because of the widespread emergence of resistance to all available drugs. Screening of the Harbor Branch enriched fraction library against the Plasmodium falciparum chloroquine-resistant strain (Dd2) followed by bioassay-guided fractionation led to the identification of two potent antiplasmodials; a novel diterpene designated as bebrycin A (1) and the known C21 degraded terpene nitenin (2). A SYBR Green I assay was used to establish a Dd2 EC50 of 1.08 ± 0.21 and 0.29 ± 0.02 µM for bebrycin A and nitenin, respectively. Further analysis was then performed to assess the stage specificity of the inhibitors antiplasmodial effects on the Dd2 intraerythrocytic life cycle. Exposure to bebrycin A was found to block parasite maturation at the schizont stage if added any time prior to late schizogony at 42 hours post invasion, (HPI). In contrast, early life cycle exposure to nitenin (prior to 18 HPI) was identified as crucial to parasite inhibition, suggesting nitenin may target the maturation of the parasite during the transition from ring to early trophozoite (6–18 HPI), a novel property among known antimalarials.
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影响因子：
5.4
作者：
Kamada T;Kang MC;Phan CS;Zanil II;Jeon YJ;Vairappan CS
通讯作者：
Vairappan CS
DOI：
10.1016/j.ijpddr.2017.02.002
发表时间：
2017-04
期刊：
International journal for parasitology. Drugs and drug resistance
影响因子：
--
作者：
Roberts BF;Zheng Y;Cleaveleand J;Lee S;Lee E;Ayong L;Yuan Y;Chakrabarti D
通讯作者：
Chakrabarti D
影响因子：
5.1
作者：
Aknin, M;Rudi, A;Gaydou, EM
通讯作者：
Gaydou, EM
DOI：
10.1385/1-59259-271-6:477
发表时间：
2002-01-01
期刊：
Methods in molecular medicine
影响因子：
--
作者：
Jensen, James B
通讯作者：
Jensen, James B
影响因子：
--
作者：
Kim, Sang Min;Kang, Suk-Woo;Pan, Cheol-Ho
通讯作者：
Pan, Cheol-Ho