Amidine- and Amidoxime-Substituted Heterocycles: Synthesis, Antiproliferative Evaluations and DNA Binding.

The novel 1,2,3-triazolyl-appended - and -heterocycles containing amidine - and amidoxime - moiety were prepared and evaluated for their antiproliferative activities in vitro. Among the series of amidine-substituted heterocycles, aromatic diamidine and coumarine amidine had the most potent growth-inhibitory effect on cervical carcinoma (HeLa), hepatocellular carcinoma (HepG2) and colorectal adenocarcinoma (SW620), with IC values in the nM range. Although compound was toxic to non-tumor HFF cells, compound showed certain selectivity. From the amidoxime series, quinoline amidoximes and showed antiproliferative effects on lung adenocarcinoma (A549), HeLa and SW620 cells emphasizing compound that exhibited no cytostatic effect on normal HFF fibroblasts. Results of CD titrations and thermal melting experiments indicated that compounds and most likely bind inside the minor groove of AT-DNA and intercalate into AU-RNA. Compounds , and bind to AT-DNA with mixed binding mode, most probably minor groove binding accompanied with aggregate binding along the DNA backbone.