主催: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
会議名: WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
開催地: Kyoto
開催日: 2018/07/01 - 2018/07/06
Introduction and Aims: The success of our first line antimalarial treatment is threatened by increased drug resistance in Plasmodium parasites. This makes the development of novel drugs critical to combat malaria. Historically, biological systems have been a good source of novel antimalarial compounds, and thus are an ideal place to search for potential drugs. Members of the bacterial phylum, Actinobacteria, are well known antibiotic producers, but their antimalarial potential has not been well investigated. This makes the actinobacteria a potentially, valuable source of novel antimalarial compounds. The aim of this investigation was to screen actinobacteria extracts for antimalarial activity and isolate and evaluate the active compounds found.
Methods: Novel actinobacteria were cultured in liquid medium until sufficient cell mass was reach. The cell mass and broth were then separated by filtration and extracted with ethyl acetate and methanol. Crude extracts were tested for in vitro antiplasmodial activity, using the parasite lactate dehydrogenase assay (pLDH) against the drug sensitive NF54 and the multi-drug resistant K1 strains of Plasmodium falciparum. Active extracts were separated by two dimensional thin layer chromatography (2D TLC), fractions were collected and tested for antiplasmodial activity. Cytotoxicity of active fractions was determined against the Chinese Hamster Ovary (CHO) cell line using the MTT assay. The active fractions were purified using solid phase extraction techniques.
Results: Three of seven actinobacterial strains tested had extracts with antimalarial activity. The strain that produced the most active extract was PR3 and was shown to be a member of the Streptomyces genus by 16S rRNA gene sequencing. Three active fractions have been isolated from strain PR3 by 2D TLC, all of which have IC50s of less than 500 ng/ml against both NF54 and K1 strains of P. falciparum. All samples were non-toxic to the CHO cell line. These four compounds are currently being purified and identified.
Conclusion: All three compounds show excellent in vitro antiplasmodial activity and host selectivity making them candidates for structural elucidation and in vivo studies.
