Synthesis and antitumour evaluation of novel 2-phenylbenzimidazoles

Figures & data

Figure 1 Antitumour benzothiazoles.

Scheme 1 Synthesis of 2-phenylbenzimidazole products 3a-k.

Figure 2 N-1/N-3 proton tautomerisation in compounds 3b, 3e and 3h, and nOe effects in products 3j and 3k.

Table I.  In vitro antitumour activity against the MCF-7 and MDA 468 breast cancer cell lines.

Compound	Mean GI50/μM^1 MCF-7^2	Mean GI50/μM^1 MDA 468^3
PMX 610^4	< 0.0001	< 0.0001
3a	59.8	>100
3b	175.7 (15.6)	94.4 (6.9)
3c	90.3 (8.5)	84.2 (19.8)
3d	50.8 (0.2)	43.6 (7.9)
3e	53.4 (4.5)	39.8 (3.8)
3f	>100	>100
3g	70.6 (4.4)	43.2 (0.5)
3h	49.4 (8.4)	26.3 (21.4)
3i	72.4 (2.5)	79.3 (16.2)
3j	6.82 (0.07)	5.19 (1.09)
3k	6.40 (0.28)	4.55 (0.40)

¹ Mean GI₅₀ (50% growth inhibition) values from experiments carried out in triplicate. Standard deviations are given in brackets² MCF-7 = Estrogen receptor positive human breast carcinoma cell line³ MDA 468 = Estrogen receptor negative human breast carcinoma cell line⁴ see reference [11].

Figure 3 Structure of carboxylic acid linked (arylsulfonyl) indole-substituted antitumour quinol 5.

CG Mortimer, G Wells, J-P Crochard, EL Stone, TD Bradshaw, MFG Stevens, and AD Westwell. (2006). Antitumor benzothiazoles. 26. 2-(3,4-Dimethoxyphenyl)-5-fluorobenzothiazole (GW 610, NSC 721648), a simple fluorinated 2-arylbenzothiazole, shows potent and selective inhibitory activity against lung, colon, and breast cancer cell lines. J Med Chem 49:179–185.

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