| Summary: | The novel 1,2,3-triazolyl-appended <i>N</i>- and <i>O</i>-heterocycles containing amidine <b>4</b>–<b>11</b> and amidoxime <b>12</b>–<b>22</b> moiety were prepared and evaluated for their antiproliferative activities in vitro. Among the series of amidine-substituted heterocycles, aromatic diamidine <b>5</b> and coumarine amidine <b>11</b> had the most potent growth-inhibitory effect on cervical carcinoma (HeLa), hepatocellular carcinoma (HepG2) and colorectal adenocarcinoma (SW620), with IC<sub>50</sub> values in the nM range. Although compound <b>5</b> was toxic to non-tumor HFF cells, compound <b>11</b> showed certain selectivity. From the amidoxime series, quinoline amidoximes <b>18</b> and <b>20</b> showed antiproliferative effects on lung adenocarcinoma (A549), HeLa and SW620 cells emphasizing compound <b>20</b> that exhibited no cytostatic effect on normal HFF fibroblasts. Results of CD titrations and thermal melting experiments indicated that compounds <b>5</b> and <b>10</b> most likely bind inside the minor groove of AT-DNA and intercalate into AU-RNA. Compounds <b>6</b>, <b>9</b> and <b>11</b> bind to AT-DNA with mixed binding mode, most probably minor groove binding accompanied with aggregate binding along the DNA backbone.
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