Transferrin coupled azanthraquinone enhances the killing effect on trypanosomes. The role of lysosomal mannosidase.
Partially purified azanthraquinone (AQ) extract from Mitracarpus scaber was coupled to bovine transferrin (Tf) using azidophenyl glyoxal (APG). The AQ-APG-Tf conjugate was found to possess an enhanced in vitro trypanocidal activity against Trypanosoma congolense and T. brucei brucei. At low concentrations of 0.39-90 mg/ml, the conjugate diminished the growth of T. congolense and T. b. brucei dose dependently at the logarithmic phase. Both parasites were more sensitive to AQ-APG-Tf than to the free (AQ) extract. Growth inhibition on the parasites by the free extract was observed at 20-200 mg/ml. The total activity of the lysosomal enzyme a-mannosidase was reduced in the T. congolense cells treated with AQ-APG-Tf in a dose related pattern. However, the activity of the mannosidase in the T. b. brucei treated cells is less affected. The AQ-APG-Tf is more effective on a mannosidase than free AQ, eight and four fold for T. congolense and T. b. brucei respectively. The results are discussed as regards the potency of using transferrin as suitable drug carrier in the chemotherapy of Human sleeping sickness.
Nok
A J
AJ
Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria. jandrew@skannet.com
Nock
I H
IH
D000818:Animals; D000880:Anthraquinones / Q000737:chemistry* / Q000494:pharmacology*; D001372:Aza Compounds / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006037:Glyoxal / Q000031:analogs & derivatives / Q000737:chemistry; D066298:In Vitro Techniques; D008247:Lysosomes / Q000201:enzymology; D008361:Mannosidases / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D019666:Rubiaceae / Q000737:chemistry*; D014168:Transferrin / Q000737:chemistry / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000201:enzymology / Q000472:pathogenicity; D014348:Trypanosoma congolense / Q000187:drug effects* / Q000201:enzymology / Q000472:pathogenicity
D000880:Anthraquinones; D001372:Aza Compounds; D010936:Plant Extracts; D014168:Transferrin; D014344:Trypanocidal Agents; D006037:Glyoxal; D008361:Mannosidases