Antiparasitic alkaloids from Psychotria klugii

J Nat Prod. 2003 Jul;66(7):962-7. doi: 10.1021/np030086k.

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 (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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkaloids* / chemistry
  • Alkaloids* / isolation & purification
  • Alkaloids* / pharmacology
  • Animals
  • Antimalarials* / chemistry
  • Antimalarials* / isolation & purification
  • Antimalarials* / pharmacology
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Drug Screening Assays, Antitumor
  • Humans
  • Inhibitory Concentration 50
  • Leishmania donovani / drug effects
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Peru
  • Plants, Medicinal / chemistry*
  • Plasmodium falciparum / drug effects*
  • Psychotria / chemistry*
  • Quinazolines / chemistry
  • Quinazolines / isolation & purification*
  • Quinazolines / pharmacology
  • Tumor Cells, Cultured / drug effects

Substances

  • 7'-O-demethylisocephaeline
  • Alkaloids
  • Antimalarials
  • Antineoplastic Agents, Phytogenic
  • Quinazolines
  • klugine