Synthesis of novel benzoxanthone analogues as non-Camptothecin topoisomerase I inhibitors

Figures & data

Scheme 1.  Reagents and conditions: (a) POCl₃, 70°C.

Scheme 2.  Reagents and conditions: (a) Br₂ (2 eq), AcOH, r.t.; (b) NIS, DMF, r.t.; (c) Br₂ (3 eq), AcOH, r.t.; (d) 2-hydroxybenzyl alcohol, ZnCl₂, 100°C, dioxane; (e) different acyl chloride, Et₃N, acetone, r.t.; (f) benzyl bromide, K₂CO₃, acetone, ref.; (g) corresponding acyl chloride, NaH, THF (dry), r.t.; (h) 3-methoxybenzoyl chloride, Et₃N, acetone, r.t., then 3-bromobenzoyl chloride, NaH, THF (dry), r.t.

Table 1.  The IC₅₀ (μM) values of the synthesized compounds against three tumour cell lines.

Compounds	A549	MDA-MB-435	HCT116
1	151.58	179.54	26.8
2	102.23	127.87	72.51
3	56.99	121.57	59.65
4	87.75	86.18	60.47
5	14.27	15.8	5.17
6a	>200	>200	117.17
6b	96.02	>200	>200
6c	57.85	>200	28.66
7a	42.8	>200	>200
7b	>200	153.19	>200
7c	>200	59.65	153.61
7d	>200	171.6	>200
7e	50.2	>200	28.94
TPT	3.16	0.448	1.1

Note: Cancer cells: A549: Lung cancer cell, HCT116: Colon cancer cell, MDA-MB-435: Breast cancer cell.

Figure 1.  Effect of the selected compounds on topoisomerase-I-mediated DNA relaxation in single concentration. Topo I was Topoisomerase I and DNA without drugs. The samples were reacted with 100 μM drugs at 37°C for 15 min. Reactions were then stopped by adding 0.5% SDS. Gels were photographed under UV transilluminator.