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<p>Marine microbes are a significant source of natural products (NPs) with marine drug development potential. In this study, we investigated NPs with antimalarial activity from <i>Streptomyces</i> sp. 13-12-16 derived from the sponge <i>Smenospongia aurea aurea</i>. Cyclo [L-Leu-F 4-hydroxy-L-Pro] (Compound A), Cyclo- 4-OH-(L)-Pro-(L)-Phe (Compound B) were isolated from <i>Streptomyces</i> sp. 13-12-16. <i>Plasmodium berghei</i> ANKA (PbA)-infected mice showed a reduction in blood parasitaemia (nearly 20% survival at 12 dpi) and an increase in body weight (60%) in the presence of the compounds Cyclo [L-Leu- 4-hydroxy-L-Pro], Cyclo [4-OH-(L)-Pro-(L)-Phe] (i.e. LK16F3 and LK3-1), the M1 subtype of peritoneal macrophages returned to normal, with an increase in phagocytic capacity and a decrease in pro-inflammatory response. TNFa-l levels were reduced after treatment with compounds LK16F3 and LK3-1, leading to a decrease in inflammation-driven immune responses. Thus, diketopiperazines compounds Cyclo [L-Leu- 4-hydroxy-L-Pro], Cyclo [4-OH-(L)-Pro-(L)-Phe](i.e. LK16F3 and LK3-1) possess enormous potential as antimalarial therapeutic regimens for cerebral malaria infection.</p>

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Diketopiperazines with In vivo Antimalarial Activity from Sponge-derived Streptomyces sp. 13-12-16

  • 期刊论文

  • 发表日期：

    2026年2月21日

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  • Loganathan Karthik,
  • Arivarasan Vishnu Kirthi,
  • Anirban Sengupta,
  • Tarun Keswani,
  • Yingxin Li,
  • Shivakumar Banakar,
  • Arindam Bhattachariya,
  • Zhiyong Li

摘要

Marine microbes are a significant source of natural products (NPs) with marine drug development potential. In this study, we investigated NPs with antimalarial activity from Streptomyces sp. 13-12-16 derived from the sponge Smenospongia aurea aurea. Cyclo [L-Leu-F 4-hydroxy-L-Pro] (Compound A), Cyclo- 4-OH-(L)-Pro-(L)-Phe (Compound B) were isolated from Streptomyces sp. 13-12-16. Plasmodium berghei ANKA (PbA)-infected mice showed a reduction in blood parasitaemia (nearly 20% survival at 12 dpi) and an increase in body weight (60%) in the presence of the compounds Cyclo [L-Leu- 4-hydroxy-L-Pro], Cyclo [4-OH-(L)-Pro-(L)-Phe] (i.e. LK16F3 and LK3-1), the M1 subtype of peritoneal macrophages returned to normal, with an increase in phagocytic capacity and a decrease in pro-inflammatory response. TNFa-l levels were reduced after treatment with compounds LK16F3 and LK3-1, leading to a decrease in inflammation-driven immune responses. Thus, diketopiperazines compounds Cyclo [L-Leu- 4-hydroxy-L-Pro], Cyclo [4-OH-(L)-Pro-(L)-Phe](i.e. LK16F3 and LK3-1) possess enormous potential as antimalarial therapeutic regimens for cerebral malaria infection.