Some benzoxazoles and benzimidazoles as DNA topoisomerase I and II inhibitors

Figures & data

Table I.  IC₅₀ values against eukaryotic DNA topoisomerase I and II for the tested compounds and the reference drugs (μM).

Comp. No:	X	Y	R	R1	IC50 (μM)^*	IC50 (μM)^**
1	O	–	H	NHCH3	NE	1130
2	O	–	NH2	H	495	580
3	O	–	NH2	F	132.3	487.8
4	O	–	Cl	CH3	1065	22.3
5	O	–	NH2	Br	134.1	NE
6	O	CH2	H	NO2	NE	17.4
7	O	CH2	Cl	OCH3	NE	200
8	O	CH2	NO2	NO2	NE	91.4
9	O	CH2	Cl	Br	NE	NE
10	O	CH2	H	Cl	443.5	NE
11	O	CH2	NH2	CH3	NE	186.7
12	NH	CH2	CH3	CH3	1765	2300
13	NH	C2H4	CH3	H	NE	1150.5
14	NH	C2H4	Cl	H	NE	917.4
15	NH	CH2O	Cl	H	NE	906.1
16	NH	CH2O	Cl	Cl	NE	799
17	NH	CH2O	H	H	14.1	NE
18	NH	CH2O	NO2	H	248	2456
Camptothecin					526	–
Etoposide					–	170

NE: Not effective; *IC₅₀ values of tested compounds and the reference drug camptothecin as DNA topoisomerase I inhibitors; ^**IC₅₀ values of tested compounds and the reference drug etoposide as DNA topoisomerase II inhibitors.

Figure 1 Electrophoregram showing the inhibitory effects of tested compound 17 and reference drug camptothecin on eukaryotic DNA topoisomerase I. Lane 1; supercoiled pBR322 plasmid DNA (0.3 μg) with incubation mixture without enzyme. Lane 2; plasmid DNA with 1 U of topo I enzyme (control). Lanes 3–6; plasmid DNA with 1 U of topo I enzyme in the presence of compound 17 at concentrations 0.1, 1, 5 and 10 μg/μL, respectively. Lane 7; plasmid DNA with compound 17 at a concentration of 10 μg/μL without enzyme. Lane 8; plasmid DNA with 1 U of topo I enzyme and a known DNA topoisomerase I inhibitor (camptothecin) at a concentration of 5 μg/μL. The relaxation assay in a cell-free system was performed as described in methods.

Figure 2 Electrophoregram showing the inhibitory effects of tested compound 6 and reference drug etoposide on eukaryotic DNA topoisomerase II. Lane 1; supercoiled pBR322 plasmid DNA (0.3 μg) with incubation mixture without enzyme. Lane 2; plasmid DNA with 5 U of topo II enzyme (control). Lanes 3–6; plasmid DNA with 5 U of topo II enzyme in the presence of compound 6 at concentrations 0.1, 1, 5 and 10 μg/μL, respectively. Lane 7; plasmid DNA with compound 6 at a concentration of 10 μg/μL without enzyme. Lane 8; plasmid DNA with 5 U of topo II enzyme and a known DNA topoisomerase II inhibitor (etoposide) at a concentration of 10 μg/μL. The relaxation assay in a cell-free system was performed as described in methods.