Microwave-assisted synthesis of sec/tert-butyl 2-arylbenzimidazoles and their unexpected antiproliferative activity towards ER negative breast cancer cells

Figures & data

Figure 1.  Some bicyclic privileged structures with cytotoxic activity against breast cell lines.

Scheme 1.  Synthesis of N-sec/tert-butyl 2-arylbenzimidazoles 10a-e and 11a-e.

Table 1.  Cyclocondensation reaction of aldehydes 9a-j under microwave conditions and analytical data of the benzimidazole products 10a-e and 11a-e.

Aldehydes 9	Aromatic substitution	Time (min)^a	Products	Yield^b (%)	Mp ^oC
a	H	2	10a	92	121
b	4-F	3	10b	94	160
c	4-Br	2	10c	96	122
d	3-NO2	3	10d	89	109
e	2-OH	2.5	10e	95	178
f	4-CH3	2	11a	91	165
g	4-OCH3	2	11b	92	156
h	2-Cl	3.5	11c	85	155
i	2,4-Cl	3	11d	87	148
j	2-OH	2	11e	93	140

^aReaction time under optimised microwave conditions. ^bIsolated yield.

Table 2  Cytotoxicity of sec-/tert-butyl 2-arylbenzimidazoles against human breast cancer cell lines.

Compound	R^2	IC50 (µM)
		MDA-MB-231^a,c MCF-7^b,d
R^1 = sec-butyl
10a	H	29.7	>200
10b	4-F	>200	>200
10c	4-Br	81.5	>200
10d	3-NO2	36.8	>200
10e	2-OH	>200	>200
R^1 = tert-butyl
11a	4-CH3	>200	>200
11b	4-OCH3	88.6	>200
11c	2-Cl	>200	>200
11d	2,4-Cl	47.6	>200
11e	2-OH	>200	>200

^aThe concentration required to inhibit the proliferation of the cells by 50% expressed as IC₅₀ (µM). Values given represent the mean obtained from three consecutive experiments. ^bIC₅₀ values could not be determined since the concentrations exceeded the range tested. ^cHormone independent human breast cancer cell line. ^dHormone dependent human breast cancer cell line.