Design and synthesis of new mitochondrial cytotoxin N-thiadiazolylanilines that inhibit tumor cell growth.

Abstract New N -thiadiazolylanilines were designed and synthesized to develop mitochondrial cytotoxins superior to SF 6847. The mitochondrial cytotoxin N -thiadiazolylanilines, TX-108 and TX-109, inhibited EMT6/KU mammary sarcoma cell growth at a low micromolar concentration. Their inhibitory activities were parallel to their mitochondrial cytotoxicity, such as uncoupling oxidative phosphorylation and inhibiting ATP synthesis. This report also supports the notion that the inhibition of tumor cell growth of inhibitor of protein tyrosine kinase AG17, which is identical to SF 6847, may be due to its mitochondrial cytotoxicity.