Derivatives of Dictyostelium differentiation-inducing factors suppress the growth of Plasmodium parasites in vitro and in vivo

Toshihiro Mita, Makoto Hirai, Yoshiko Maki, Saifun Nahar, Naoko Yoshida, Yoshiteru Oshima, Haruhisa Kikuchi, Yuzuru Kubohara

研究成果: Article査読

抄録

Malaria, which is caused by protozoa of the genus Plasmodium, remains a major endemic public health problem worldwide. Since artemisinin combination therapies are used as a first-line treatment in all endemic regions, the emergence of parasites resistant to these regimens has become a serious problem. Differentiation-inducing factor 1 (DIF-1) is a chlorinated alkylphenone originally found in the cellular slime mold Dictyostelium discoideum. DIF-1 and its derivatives exhibit a range of biological activities. In the present study, we investigated the effects of 41 DIF derivatives on the growth of Plasmodium falciparum in vitro using four laboratory strains and 12 field isolates. Micromolar concentrations of several DIF derivatives strongly suppressed the growth of the four laboratory strains, including strains that exhibited resistance to chloroquine and artemisinin, as well as strains that were susceptible to these drugs. In addition, DIF-1(+2), the most potent derivative, strongly suppressed the growth of 12 field isolates. We also examined the effects of DIF-1(+2) on the activity of the rodent malarial parasite Plasmodium berghei in mice. Intraperitoneal administration of DIF-1(+2) over 4 days (50 or 70 mg/kg/day) significantly suppressed the growth of the parasite in the blood with no apparent adverse effects, and a dose of 70 mg/kg/day significantly prolonged animal survival. These results suggest that DIF derivatives, such as DIF-1(+2), could serve as new lead compounds for the development of antimalarial agents.

本文言語English
論文番号114834
ジャーナルBiochemical Pharmacology
194
DOI
出版ステータスPublished - 2021 12月
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 薬理学

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