The effect of two novel analogues of antimycin A on oxygen consumption and survival of filarial nematodes in vitro.
The effects of two novel analogues of antimycin A (BWA466C and BWA728C) on filarial oxygen consumption, energy generation and survival were investigated in vitro. For comparison, incubations were performed with a range of mitochondrial respiration inhibitors. All compounds tested (rotenone, antimycin A, KCN, oligomycin, CCCP, rafoxanide, BWA466C and BWA728C) inhibited oxygen uptake. The two analogues were less potent than antimycin A at impairing respiration of either filariae or beef heart submitochondrial particles. However, the two compounds affected motility and were lethal in vitro. Although the analogues affected oxygen uptake similarly to antimycin A itself, the levels of ATP were significantly lower than those noted in the presence of antimycin A. Glucose consumption and lactate output were markedly reduced by BWA466C and BWA728C. Glucose transport (measured as 2-deoxy-[2,6-3H]glucose) was reduced after treatment with BWA728C. It is likely that a combination of the effects on glucose transport and inhibition of oxidative pathways of carbohydrate metabolism may lead to worm death in vitro.
Hayes
D J
DJ
Biochemical Sciences, Wellcome Research Laboratories, Beckenham, Kent, U.K.
O'Dowd
A B
AB
Selwood
D L
DL
Stables
J N
JN
Comley
J C
JC
Rees
M J
MJ
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D002009:Brugia / Q000187:drug effects*; D050260:Carbohydrate Metabolism; D002417:Cattle; D004153:Dipetalonema / Q000187:drug effects* / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects
D000227:Adenine Nucleotides; D000969:Antinematodal Agents; D001549:Benzamides; C063599:BWA 466C; C063600:BWA 728C