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Pyronaridine: A new antimalarial drug.

S Fu1, S H Xiao

  • 1Institute of Parasitic Diseases, Chinese Academy of Preventive Medicine, 207 Rui Jin Er Lu, Shanghai 200025, People's Republic of China.

Parasitology Today (Personal Ed.)
|November 1, 1991
PubMed
Summary

Pyronaridine, a new antimalarial drug developed in China, shows efficacy against chloroquine-resistant Plasmodium falciparum. Research also explores drug combinations to combat resistance, offering hope for tropical regions.

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Area of Science:

  • Pharmacology and Tropical Medicine
  • Drug Discovery and Development

Background:

  • Widespread chloroquine-resistant Plasmodium falciparum necessitates novel antimalarial drugs, especially for tropical countries.
  • Pharmaceutical industry withdrawal from tropical disease research creates a critical need for alternative drug development.
  • Chinese research efforts have focused on developing pyronaridine as a potential chloroquine alternative.

Purpose of the Study:

  • To summarize research on pyronaridine, an antimalarial drug effective against multiply resistant Plasmodium.
  • To highlight the development of pyronaridine from Chinese research efforts, largely published in Chinese literature.
  • To investigate strategies, including drug combinations, to overcome or delay pyronaridine resistance.

Main Methods:

  • Pyronaridine development involved 30 years of chemistry, starting with the mepacrine nucleus.
  • Extensive synthesis and screening of mepacrine derivatives led to the identification of optimal substitutions.
  • Combination therapies, including triple combinations and pyronaridine-primaquine, were investigated.

Main Results:

  • Pyronaridine, derived from mepacrine with an amodiaquine side-chain, demonstrates high activity with fewer adverse effects.
  • Pyronaridine is an active blood schizonticide, effective against chloroquine-resistant Plasmodium strains in human trials.
  • Paradoxically, pyronaridine-resistant Plasmodium exhibits resistance to chloroquine.

Conclusions:

  • Pyronaridine represents a significant advancement in antimalarial drug development, particularly for chloroquine-resistant malaria.
  • Ongoing research into drug combinations aims to mitigate the rapid development of pyronaridine resistance.
  • Further investigation is needed to understand pyronaridine's mode of action and the basis of resistance development.

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