Biological activity of bis-benzimidazole derivatives on DNA topoisomerase I and HeLa, MCF7 and A431 cells

Figures & data

Table I.  Physical constants of the synthesized compounds.

Compound	R	R1	X	m.p. (°C)	Yield (%)	Mol. formula
1	H	H	CH2	295–298	25.6	C15H12N4
2	CH3	H	CH2	283–286	7.5	C17H16N4
3	CH3	CH3	CH2	278–283	7.1	C19H20N4
4	H	H	(CH2)2	344–345	69.0	C16H14N4
5	CH3	H	(CH2)2	271	22.0	C18H18N4
6	CH3	CH3	(CH2)2	275–276	19.0	C20H22N4
7	H	H	(CH2)3	267	37.2	C17H16N4
8	CH3	H	(CH2)3	120	16.8	C19H20N4
9	CH3	CH3	(CH2)3	296	21.7	C21H24N4
10	H	H	(CH2)4	331	93.3	C18H18N4
11	CH3	H	(CH2)4	230	17.6	C20H22N4
12	CH3	CH3	(CH2)4	142	23.0	C22H26N4

Figure 1.  Inhibitory activity of compounds 1-12 on DNA topoisomerase I. A. A representative assay using 1 μg/μL concentration of the test compounds in topo I reactions., lane 1, pBR322 DNA without enzyme; lane 2, pBR322 with 1 unit of DNA topoisomerase I; lane 3, same as lane 2 in DMSO; lanes 4-15, same as lane 2 in the presence of the test compounds from 1 to 12, respectively. B. Quantitative assessment of the inhibition obtained with the compounds.

Table II.  Calculated IC₅₀ values in MTT tests.

	Calculated IC50 values (μM)
Test Compound	A431	HeLa	MCF7
Cpd.3	3.74	13.98	3.58
Doxorubicin	0.19	0.16	0.31