Reports
Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 3 309
Table 3. Synthesis of Cinnamic Amides via Silica Gel-Mediated Reactiona and Cytotoxic Activities in Vitrob (IC50, µM)
entry
amine (II)
m-anisidine
m-toluidine
o-anisidine
yield (%)
HepG2
Hep-2
EJ
Raji
54.5
IV-1
IV-2
IV-3
IV-4
IV-5
IV-6
IV-7
IV-8
IV-9
IV-10
DDP
75
69
72
76
67
78
66
85
90
72
27.9
47.6
69.5
36.3
46.1
>100
11.2
>100
>100
>100
>100
>100
>100
18
26.8
84.7
53.8
12.0
>100
>100
aniline
9.0
16.9
2-aminopyridine
1-adamantylamine
4-methoxyphenylethanamine
cyclohexylamine
morpholine
>100
>100
>100
>100
>100
>100
13.6
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
>100
diethylamine
7.9
4.1
a Yields represent isolated yield. b Cytotoxicity, as IC50 for each cell line, is the concentration of compound which reduced by 50% the optical
density of treated cells with respect to untreated cells using the MTT assay.
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of all synthesized cinnamic amides was evaluated in vitro
against liver carcinoma (HepG2), laryngeal carcinoma
(Hep-2), bladder carcinoma (EJ), and lymphoma (Raji).
Cisplatin (DDP) was used as the reference drug. The
results of the cytotoxicity studies are summarized in Table
3. The results of the cytotoxicity studies showed that
arylamines (IV-1-IV-5) exhibited higher cytotoxic activi-
ties than alkylamines (IV-6-IV-10). From Table 3, it has
been found that cinnamic amide IV-4 displayed significant
potency with the in vitro cytotoxic activities comparable
to DDP. Additionally, cinnamic amide IV-1 (III-17)
exhibited moderate cytotoxic activities.
In conclusion, an efficient, functional group tolerant, and
environmentally benign process for the synthesis of amides
was developed. Our protocol provides an alternative for the
combinatorial liquid-phase synthesis of amide libraries for
drug discovery. No activation reagents or scavengers are
required in this process. Purification of desired compounds
is easy, and cost-effective. By this method, a number of
amides were prepared and evaluated in vitro against a panel
of human tumor cell lines. Cinnamic amide IV-4 was found
to be the most potent compound synthesized against four
human tumor cell lines. Further utilization of this method
for the synthesis of complex and active amides is under
investigation.
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Acknowledgment. This work was supported by a grant
(2009CB522300) from National Basic Research Program of
China (973 Program) and a grant (2007B0006Z) from the
Natural Science Foundation of Yunnan Province, which are
gratefully acknowledged.
Supporting Information Available. General procedures
for the preparation of amides and spectroscopic data for all
products. This material is available free of charge via the
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References and Notes
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