Antimalarial alkaloid from Hypoestes forskaolii

Area of Science:

• Pharmacognosy
• Medicinal Chemistry
• Parasitology

Background:

• Malaria remains a significant global health challenge, necessitating the discovery of novel anti-malarial agents.
• Chloroquine resistance in Plasmodium falciparum complicates treatment strategies.
• Ethnobotanical surveys are crucial for identifying potential new drug leads from natural sources.

Purpose of the Study:

• To investigate Saudi Arabian plants for potential anti-malarial compounds.
• To isolate and characterize active compounds from promising plant extracts.
• To evaluate the efficacy and selectivity of isolated compounds against Plasmodium falciparum.

Main Methods:

• Preparation and in vitro screening of methanolic extracts from eighteen Saudi plants against Plasmodium falciparum K1.
• Cytotoxicity assessment of extracts and isolated compounds against MRC5 human diploid embryonic lung cells.
• Bio-guided fractionation of Hypoestes forskaolii extract to isolate the active alkaloid.

Main Results:

• Moderate anti-malarial activity was observed for Hypoestes forskaolii and Rhus retinorrhaea extracts.
• A novel phenanthro-quinolizidine alkaloid, 15β-hydroxycryptopleurine-N-oxide, was isolated from H. forskaolii.
• The isolated alkaloid demonstrated potent anti-malarial activity against both chloroquine-resistant (K1) and sensitive (FCR3) P. falciparum strains with low nanomolar IC50 values.
• The compound exhibited favorable selectivity indices, indicating a good therapeutic window.

Conclusions:

• Hypoestes forskaolii is a promising source of anti-malarial compounds.
• 15β-hydroxycryptopleurine-N-oxide is a novel and potent anti-malarial agent with activity against chloroquine-resistant Plasmodium falciparum.
• This study represents the first report on the anti-malarial activity of phenanthro-quinolizidine alkaloids against chloroquine-resistant malaria parasites.