Antitumor and Anti-Pneumocystis Carinii Activities of Novel Bisbenzamidines

Among a library of 17 bisbenzamidines connected with various linkers, compounds with a flexible pentanediamide (10) or hexanediamide (12) linker were the most potent derivatives against rat Pneumocystis carinii (IC₅₀ values of 3 and 2 nM, respectively) and had the highest selectivity index ratios (GI₅₀ of human tumor cells/IC₅₀ of rat P. carinii cells) of >10⁴. Seven compounds caused 50% growth inhibition (GI₅₀) of tumor cells at concentrations of <100 μM while the remaining ten were not cytotoxic. DNA binding affinity (ΔT_m) of the tested compounds did not correlate with either their anti-P. carinii activity or cytotoxicity.