Synthesis and antimalarial activity of prodigiosenes.
Several analogues of the natural compound prodigiosin with modified A- and C-rings were synthesised as were some of their tin, cobalt, boron and zinc complexes. The antimalarial activity of these prodigiosenes was evaluated in vitro using the 3D7 Plasmodium falciparum strain. The presence of a nitrogen atom in the A-ring is needed for antimalarial activity but the presence of an alkyl group at the β'-position of the C-ring seems detrimental. Dibutyl tin complexes exhibit IC50 values mostly in the nanomolar range with equal or improved activity compared to the free-base prodigiosene ligand, despite the fact that the general toxicity of such tin complexes is demonstrably lower than that of the free-bases.
Department of Chemistry, Dalhousie University, PO BOX 15000, Halifax, NS B3H 4R2, Canada. Alison.Thompson@dal.ca.
Estelle
E
Marchal
Deborah A
DA
Smithen
Md Imam
MI
Uddin
Andrew W
AW
Robertson
David L
DL
Jakeman
Vanessa
V
Mollard
Christopher D
CD
Goodman
Kristopher S
KS
MacDougall
Sherri A
SA
McFarland
Geoffrey I
GI
McFadden
Alison
A
Thompson
D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D011353:Prodigiosin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014001:Tin / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
D000962:Antimalarials; D056831:Coordination Complexes; D014001:Tin; D015032:Zinc; D011353:Prodigiosin