从放线菌培养库中的次级代谢物中发现抗疟疾药物。

IF 3.6 Q1 TROPICAL MEDICINE
Awet Alem Teklemichael, Aiko Teshima, Asahi Hirata, Momoko Akimoto, Mayumi Taniguchi, Gholam Khodakaramian, Takashi Fujimura, Fuyuki Tokumasu, Kenji Arakawa, Shusaku Mizukami
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引用次数: 0

摘要

背景:天然产物作为生物活性物质的潜在来源,在新药研发中发挥着关键作用。本研究旨在从放线菌文库提取物中鉴定对恶性疟原虫(P. falciparum)无性阶段有效的次级代谢物:方法:放线菌文库提取物中的次生代谢物通过乙酸乙酯萃取从培养上清液中分离出来。对放线菌文库提取物(n = 28)进行了全面筛选,以确定新型抗疟化合物。首先在体外对恶性疟原虫的氯喹/甲氟喹敏感株(3D7)和抗性株(Dd2)进行了抗疟活性评估。然后在原代小鼠脑(AMB)细胞中评估其细胞毒性:结果:在 28 种放线菌提取物中,有 17 种在 50 微克/毫升的浓度下对寄生虫的生长抑制率大于 50%,其中 9 种的 IC50 值分别为 0.39、0.09、0.97 和 0.36 微克/毫升(针对 3D7 株系)以及 0.26、0.22、0.72 和 0.21 微克/毫升(针对 Dd2 株系)。其中,抗生素链霉菌菌株 HUT6035 (8) 的抗疟活性最高,对 3D7 的 IC50 值为 0.09 µg/mL,对 Dd2 的 IC50 值为 0.22 µg/mL,选择性指数(SI)分别为 188 和 73.7:从放线菌提取物中获得的次生代谢物在体外对恶性疟原虫3D7和Dd2细胞系表现出良好的抗疟活性,且毒性极低。因此,从放线菌提取物中获得的次生代谢物是开发抗疟药物线索的绝佳起点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Discovery of antimalarial drugs from secondary metabolites in actinomycetes culture library.

Background: Natural products play a key role as potential sources of biologically active substances for the discovery of new drugs. This study aimed to identify secondary metabolites from actinomycete library extracts that are potent against the asexual stages of Plasmodium falciparum (P. falciparum).

Methods: Secondary metabolites from actinomycete library extracts were isolated from culture supernatants by ethyl acetate extraction. Comprehensive screening was performed to identify novel antimalarial compounds from the actinomycete library extracts (n = 28). The antimalarial activity was initially evaluated in vitro against chloroquine/mefloquine-sensitive (3D7) and-resistant (Dd2) lines of P. falciparum. The cytotoxicity was then evaluated in primary adult mouse brain (AMB) cells.

Results: Out of the 28 actinomycete extracts, 17 showed parasite growth inhibition > 50% at a concentration of 50 µg/mL, nine were identified with an IC50 value < 10 µg/mL, and seven suppressed the parasite significantly with an IC50 value < 5 µg/mL. The extracts from Streptomyces aureus strains HUT6003 (Extract ID number: 2), S. antibioticus HUT6035 (8), and Streptomyces sp. strains GK3 (26) and GK7 (27), were found to have the most potent antimalarial activity with IC50 values of 0.39, 0.09, 0.97, and 0.36 µg/mL (against 3D7), and 0.26, 0.22, 0.72, and 0.21 µg/mL (against Dd2), respectively. Among them, Streptomyces antibioticus strain HUT6035 (8) showed the highest antimalarial activity with an IC50 value of 0.09 µg/mL against 3D7 and 0.22 µg/mL against Dd2, and a selective index (SI) of 188 and 73.7, respectively.

Conclusion: Secondary metabolites obtained from the actinomycete extracts showed promising antimalarial activity in vitro against 3D7 and Dd2 cell lines of P. falciparum with minimal toxicity. Therefore, secondary metabolites obtained from actinomycete extracts represent an excellent starting point for the development of antimalarial drug leads.

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来源期刊
Tropical Medicine and Health
Tropical Medicine and Health TROPICAL MEDICINE-
CiteScore
7.00
自引率
2.20%
发文量
90
审稿时长
11 weeks
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