Borrelidin analogues with antimalarial activity: Design, synthesis and biological evaluation against Plasmodium falciparum parasites

Akihiro Sugawara; Toshiaki Tanaka; Tomoyasu Hirose; Aki Ishiyama; Masato Iwatsuki; Yoko Takahashi; Kazuhiko Otoguro; Satoshi Omura; Toshiaki Sunazuka

doi:10.1016/j.bmcl.2013.02.075

Borrelidin analogues with antimalarial activity: Design, synthesis and biological evaluation against Plasmodium falciparum parasites

Akihiro Sugawara, Toshiaki Tanaka, Tomoyasu Hirose, Aki Ishiyama, Masato Iwatsuki, Yoko Takahashi, Kazuhiko Otoguro, Satoshi Omura, Toshiaki Sunazuka

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

Abstract

Borrelidin, a structurally unique 18-membered macrolide, was found to express antimalarial activity against drug-resistant Plasmodium falciparum malaria parasites, with IC₅₀ value of 0.93 ng/mL. However, it also displays strong cytotoxicity against human diploid embryonic MRC-5 cells. To investigate the issue of the cytotoxicity of borrelidin, borrelidin-based analogues were synthesized and their anti-Plasmodium properties were evaluated. In this communication, we report that a novel borrelidin analogue, bearing the CH₂SPh moiety via a triazole linkage, was found to retain a potent antimalarial activity, against drug-sensitive and drug-resistant parasite strains, but possess only weak cytotoxicity against human cells.

Original language	English
Pages (from-to)	2302-2305
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2013.02.075
Publication status	Published - 2013 Apr 15
Externally published	Yes

Keywords

Antimalarial
Borrelidin
Malaria
Plasmodium falciparum
Structure-activity relationships

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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Borrelidin analogues with antimalarial activity : Design, synthesis and biological evaluation against Plasmodium falciparum parasites. / Sugawara, Akihiro; Tanaka, Toshiaki; Hirose, Tomoyasu; Ishiyama, Aki; Iwatsuki, Masato; Takahashi, Yoko; Otoguro, Kazuhiko; Omura, Satoshi; Sunazuka, Toshiaki.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 8, 15.04.2013, p. 2302-2305.

Research output: Contribution to journal › Article › peer-review

Sugawara, Akihiro ; Tanaka, Toshiaki ; Hirose, Tomoyasu ; Ishiyama, Aki ; Iwatsuki, Masato ; Takahashi, Yoko ; Otoguro, Kazuhiko ; Omura, Satoshi ; Sunazuka, Toshiaki. / Borrelidin analogues with antimalarial activity : Design, synthesis and biological evaluation against Plasmodium falciparum parasites. In: Bioorganic and Medicinal Chemistry Letters. 2013 ; Vol. 23, No. 8. pp. 2302-2305.

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abstract = "Borrelidin, a structurally unique 18-membered macrolide, was found to express antimalarial activity against drug-resistant Plasmodium falciparum malaria parasites, with IC50 value of 0.93 ng/mL. However, it also displays strong cytotoxicity against human diploid embryonic MRC-5 cells. To investigate the issue of the cytotoxicity of borrelidin, borrelidin-based analogues were synthesized and their anti-Plasmodium properties were evaluated. In this communication, we report that a novel borrelidin analogue, bearing the CH2SPh moiety via a triazole linkage, was found to retain a potent antimalarial activity, against drug-sensitive and drug-resistant parasite strains, but possess only weak cytotoxicity against human cells.",

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AU - Iwatsuki, Masato

AU - Takahashi, Yoko

AU - Otoguro, Kazuhiko

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