Synthesis and antitumor activity of novel benzimidazole-5-carboxylic acid derivatives and their transition metal complexes as topoisomerease II inhibitors

N-Aminomethyl-1H-benzimidazole-5-carboxylic acid derivatives 2–5 and the ligand, 1-(5 (or 6-)-carboxy-1H-benzimidazol-2-ylmethyl)pyridinium chloride (6; H2L1) have been synthesized. New benzimidazole complexes 7–9 of the ligand 6; H2L1 with Cu2+, Co2 and Zn2+ were prepared. The growth-inhibitory against a panel of 21 human cancer cell lines of the synthesized compounds 1–9 was studied. Compounds 6–9 showed potent growth-inhibitory activity against the studied cell lines. The correlation coefficients according to COMPARE analysis of the National Cancer Institute screening protocol showed that the pattern of the growth-inhibitory effect of the compounds 6–9 was similar to that of etoposide and doxorubicin but different from that of SN-38 and cisplatin. The topoisomerase II inhibitory activity of the tested compounds 6–9 was studied. Compounds 6 and 8 inhibited topoisomerase II activity at 10 times lower concentration than etoposide in relaxation assay.

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