SMQ-V047 N-002_ligas_size.pdf - Journal of the Mexican Chemical ...

Cytotoxic Evaluation of a Series of Bisalkanoic Anilides and Bisbenzoyl Diamines 187
Table 1. Physical properties, spectroscopic data and inhibition of the growth of compounds 6-27 at concentration 31 µM.
Comp. R n M.W. Yield (%) m.p. Ref. (a) K562 PC-3 U251
No. (b) (c) (d)
6 F 2 304 65 243-245 [10] 57 25 0
7 Br 2 426 69 281-282 [10,11, 12] 40 6 0
8 OMe 2 328 80 255-256 [10] 22 13 10
9 OH 2 300 92 273-274 [13] 0 13 0
10 H 2 268 83 231-232 [10, 12] 0 16 0
11 Br 3 318 70 254-256 [10] 55 0 4
12 F 4 332 65 230-233 — 96 10 39
13 Cl 4 365 75 255-256 [10] 13 0 0
14 Br 4 454 75 287-288 [12] 5 0 3
15 I 4 548 77 — 0 0 0
16 OMe 4 356 89 233-235 [10, 14] 74 18 17
17 OH 4 328 96 [13, 15] 80 34 4
18 H 4 296 95 244-245 [10, 12] 24 18 0
19 HNCOCH 3 4 410 80 > 350 — 0 0 0
20 CN 4 346 85 272-233 [14] 9 13 42
21 Br — 440 75 268-270 — 83 72 100
22 Br — 426 80 281-283 — 0 0 5
23 NO 2 — 358 80 253-254 — 0 8 0
24 NH 2 — 298 85 284-285 — 0 3 0
25 NO 2 — 372 75 235-237 — 0 26 0
26 Br — 452 89 270-273 — 0 0 6
27 NO 2 — 384 95 318-320 [16] 0 4 0
(a) References of the synthesis for previously reported compounds. (b) Leukemia (c) Prostate (d) CNS.
O
H
H 2 N
H
N
Me
N
N
H
H
N
O
H
N
O
N
Me
NH 2
1
N
Me
2
H
R N
N
O S
3
HN
O
HN
O
R'
O
n
H NH
N
2
N
Me
O
N
Me
O
H 2 N
H 2 N
H NH
N
2
H 2 N
H 2 N
H 2 N
H
N
O
O
HN
HN
O
4
H
( )n N
O
5
HN
O
HN
( )n
HN
O
Fig. 1. Examples of compounds containing polyamide and polyaromatic
functional groups along the DNA recognizing chain.
HN
O
O
NH 2
NH 2
R
COCl
R
23
COCl
R
ClCO(CH 2 )nCOCl
H 2 N
R'
H
N
N
H
NH 2
R
R
R
H
N
O
O
O
N
H
N
( )n
6-20
R'
H
N
O
H
N
N
O
O
21,25 R'=Me
22,23 R'=H
O
Pd / C
H
N
N
NH 2 NH 2 H
O
H 2 N
24
26-27
Fig. 2. Synthesis of compounds 6-27. (R values are reported on Table
1.)
R
R
R
NH 2
To study the influence of the length of the aliphatic chain
on cytotoxic activity, we prepared compounds with a four
methylene chain (12, 14, 16-18). It should be pointed out that
compounds 13 (R = Cl) and 15 (R = I) were included due to
the apparent tendency of halogens to present activity. In addition,
compounds 19 (R = NHCOCH 3 ) and 20 (R = CN) were
included in the study to investigate the effects of the
NHCOCH 3 and CN functional groups. In contrast to the
almost complete lack of activity shown by the first series (n =
2), compound 12 (R = F) induced almost 100 % inhibition of
growth in K562 cell line and the functional groups OMe (16)
and OH (17) were found to enhance cytotoxicity. The rest of
the compounds showed no activity.