DNDI-6174 is a highly potent inhibitor of Leishmania cytochrome bc1 complex activity, shows broad activity against a panel of representative visceral leishmaniasis clinical isolates from various sources (EC50=10-360 nM).
DNDI-6174 is active against clones resistant to currently used therapeutics, such as paromomycin (PM) and miltefosine (MIL).
DNDI-6174 shows high potency against T. cruzi (Tulahuen strain, EC50 value of <5 nM), the causative agent of Chagas disease, considerably less active against T. brucei brucei and T. brucei rhodesiense (bloodstream form) associated with human African trypanosomiasis, with EC50 values ranging from 5 to 20 μM.
DNDI-6174 targets the Qi site of L donovani cytochrome b.
DNDI-6174 is a potent inhibitor of complex III in lysates prepared from both promastigote and axenic amastigote stages of L. donovani with IC50 of 8 nM and 2 nM respectively.
DNDI-6174 shows potent in vitro antileishmanial activity against a range of Leishmania species responsible for causing VL or CL and current drug-resistant species and clinical isolates.
DNDI-6174 (12.5 mg/kg twice daily or 25 mg/kg once daily) decreased the liver parasite burden of infected BALB/c mice.