Azaterphenyl diamidines as antileishmanial agents.

Hu, L., R. K. Arafa, M. A. Ismail, T. Wenzler, R. Brun, M. Munde, D. W. Wilson, S. Nzimiro, S. Samyesudhas, K. A. Werbovetz, et al., "Azaterphenyl diamidines as antileishmanial agents.", Bioorganic & medicinal chemistry letters, vol. 18, issue 1, pp. 247-51, 2008 Jan 1.


Eighteen diamidino azaterphenyls and analogues were evaluated as anti-leishmanials; nine of the compounds gave IC50 values less than 1 microM, five exhibited values less than 0.40 microM, and two gave values less than 0.10 microM in a Leishmania donovani axenic amastigote assay. The activity of the diamidines strongly depends on the ring N-atom location relative to the amidine groups and correlates with DNA affinity. Transmission electron microscopy studies showed a dramatic dilation of the mitochondrion and evidence of disintegration of the kinetoplast of the amastigotes.