Antiparasitic alkaloids from Psychotria klugii.
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 (IC(50) 0.03 microg/mL) and was >20- and >5-fold more potent than pentamidine and amphotericin B, respectively, while klugine (1) (IC(50) 0.40 microg/mL) and isocephaeline (4) (IC(50) 0.45 microg/mL) were <13- and <15-fold less potent than 3. In addition, emetine (6) (IC(50) 0.03 microg/mL) was found to be as equally potent as 3, but was >12-fold more toxic than 3 against VERO cells (IC(50) 0.42 vs 5.3 microg/mL). Alkaloids 1 and 3 exhibited potent antimalarial activity against Plasmodium falciparum clones W2 and D6 (IC(50) 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.
Muhammad
Ilias
I
National Center for Natural Products Research and Department of Pharmacology, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi 38677, USA. milias@olemiss.edu
Dunbar
D Chuck
DC
Khan
Shabana I
SI
Tekwani
Babu L
BL
Bedir
Erdal
E
Takamatsu
Satoshi
S
Ferreira
Daneel
D
Walker
Larry A
LA
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010568:Peru; D010946:Plants, Medicinal / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects*; D032069:Psychotria / Q000737:chemistry*; D011799:Quinazolines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
C480053:7'-O-demethylisocephaeline; D000470:Alkaloids; D000962:Antimalarials; D000972:Antineoplastic Agents, Phytogenic; D011799:Quinazolines; C480052:klugine