Antiparasitic Alkaloids from Psychotria klugii

Abstract

Psychotria klugii yielded two new benzoquinolizidine alkaloids, klugine (1) and 7‘-O-demethylisocephaeline (2), together with the previously known cephaeline (3), isocephaeline (4), and 7-O-methylipecoside (5). The structures and stereochemistry of 1 and 2 were determined by 1D and 2D NMR data and circular dichroism experiments. Cephaeline (3) demonstrated potent in vitro antileishmanial activity against Leishmania donavani (IC₅₀ 0.03 μg/mL) and was >20- and >5-fold more potent than pentamidine and amphotericin B, respectively, while klugine (1) (IC₅₀ 0.40 μg/mL) and isocephaeline (4) (IC₅₀ 0.45 μg/mL) were 50 0.03 μg/mL) was found to be as equally potent as 3, but was >12-fold more toxic than 3 against VERO cells (IC₅₀ 0.42 vs 5.3 μg/mL). Alkaloids 1 and 3 exhibited potent antimalarial activity against Plasmodium falciparum clones W2 and D6 (IC₅₀ 27.7−46.3 ng/mL). Compound 3 was cytotoxic to SK-MEL, KB, BT-549, and SK-OV-3 human cancer cells, while 1 was inactive.