The usefulness of cyclic diamidines with different core-substituents as antitumor agents

A series of related polycationic compounds has been screened for potential antitumor activity by the NCI’s in vitro testing (one dose primary anticancer assay and the NCI-60 full panel screening). The GI50 values of triazines 3 and 4 are on average 1.9 μM and 2.4 μM, respectively. Furan 8 deserves mention too (1.9 μM). The biological test results showed that carbazole 10 possessed cytotoxic activity in the nanomolar range, much better than the other compounds tested, only against several cancer cell lines: CCRF-CEM, HL-60(TB), MOLT-4, NCI-H522, COLO 205, SF-268, but the average GI50 value was higher (15 μM). The activity appears closely dependent on the core-shape and length of the bisimidazoline molecules (important for both high cytotoxicity and DNA binding). The mechanism of DNA minor-groove binding of diamidines 1–12, based on the anticancer parameters, is highly probable.

The NCI’s anticancer parameters of the polycationic agents investigated depend on the hydrogen bonding effects (N-atom distances, core-shape and length) and correlate with DNA affinity.Figure optionsDownload as PowerPoint slide