Isolation and in vitro antiplasmodial activities of alkaloids from Teclea trichocarpa: in vivo antimalarial activity and X-ray crystal structure of normelicopicine.
Seven alkaloids have been isolated from Teclea trichocarpa including four, normelicopicine (1), arborinine (2), skimmianine (6), and dictamnine (7), that are reported for the first time in addition to the previously reported alkaloids melicopicine (3), tecleanthine (4), and 6-methoxytecleanthine (5). The structure of 1 was confirmed by single-crystal X-ray crystallography. Two alkaloids, 1 and 2, displayed limited in vitro activities against Plasmodium falciparum strains HB3 and K1, but there appeared to be little cross-resistance with chloroquine. Alkaloid 1 was found to have some activity against P. berghei in mice (32% suppression of parasitaemia at a dose of 25 mg x kg(-1) x day(-1)), but unlike chloroquine it did not inhibit beta-haematin formation in a cell-free system; 1 was found to have low in vitro cytotoxicity to KB cells (IC50 > 328 microM).
Department of Chemistry, University of Nairobi, Box 30197, Nairobi, Kenya.
Mary W
MW
Muriithi
W-R
WR
Abraham
Jonathan
J
Addae-Kyereme
Ian
I
Scowen
Simon L
SL
Croft
Peter M
PM
Gitu
Howard
H
Kendrick
E N M
EN
Njagi
Colin W
CW
Wright
D000166:Acridines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002738:Chloroquine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004912:Erythrocytes; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007624:KB Cells / Q000187:drug effects; D007630:Kenya; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D015394:Molecular Structure; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects*; D011804:Quinolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D027821:Rutaceae / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
C465801:6-methoxy-tecleanthine; D000166:Acridines; D000470:Alkaloids; D000962:Antimalarials; D011804:Quinolines; C465802:melicopicine; C465799:normelicopicine; C465800:tecleanthine; C035932:skimmianine; C022784:arborinine; C023676:chloroquine diphosphate; D002738:Chloroquine