SMQ-V047 N-002_ligas_size.pdf - Journal of the Mexican Chemical ...
SMQ-V047 N-002_ligas_size.pdf - Journal of the Mexican Chemical ...
SMQ-V047 N-002_ligas_size.pdf - Journal of the Mexican Chemical ...
Create successful ePaper yourself
Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.
Cytotoxic Evaluation <strong>of</strong> a Series <strong>of</strong> Bisalkanoic Anilides and Bisbenzoyl Diamines 187<br />
Table 1. Physical properties, spectroscopic data and inhibition <strong>of</strong> <strong>the</strong> growth <strong>of</strong> compounds 6-27 at concentration 31 µM.<br />
Comp. R n M.W. Yield (%) m.p. Ref. (a) K562 PC-3 U251<br />
No. (b) (c) (d)<br />
6 F 2 304 65 243-245 [10] 57 25 0<br />
7 Br 2 426 69 281-282 [10,11, 12] 40 6 0<br />
8 OMe 2 328 80 255-256 [10] 22 13 10<br />
9 OH 2 300 92 273-274 [13] 0 13 0<br />
10 H 2 268 83 231-232 [10, 12] 0 16 0<br />
11 Br 3 318 70 254-256 [10] 55 0 4<br />
12 F 4 332 65 230-233 — 96 10 39<br />
13 Cl 4 365 75 255-256 [10] 13 0 0<br />
14 Br 4 454 75 287-288 [12] 5 0 3<br />
15 I 4 548 77 — 0 0 0<br />
16 OMe 4 356 89 233-235 [10, 14] 74 18 17<br />
17 OH 4 328 96 [13, 15] 80 34 4<br />
18 H 4 296 95 244-245 [10, 12] 24 18 0<br />
19 HNCOCH 3 4 410 80 > 350 — 0 0 0<br />
20 CN 4 346 85 272-233 [14] 9 13 42<br />
21 Br — 440 75 268-270 — 83 72 100<br />
22 Br — 426 80 281-283 — 0 0 5<br />
23 NO 2 — 358 80 253-254 — 0 8 0<br />
24 NH 2 — 298 85 284-285 — 0 3 0<br />
25 NO 2 — 372 75 235-237 — 0 26 0<br />
26 Br — 452 89 270-273 — 0 0 6<br />
27 NO 2 — 384 95 318-320 [16] 0 4 0<br />
(a) References <strong>of</strong> <strong>the</strong> syn<strong>the</strong>sis for previously reported compounds. (b) Leukemia (c) Prostate (d) CNS.<br />
O<br />
H<br />
H 2 N<br />
H<br />
N<br />
Me<br />
N<br />
N<br />
H<br />
H<br />
N<br />
O<br />
H<br />
N<br />
O<br />
N<br />
Me<br />
NH 2<br />
1<br />
N<br />
Me<br />
2<br />
H<br />
R N<br />
N<br />
O S<br />
3<br />
HN<br />
O<br />
HN<br />
O<br />
R'<br />
O<br />
n<br />
H NH<br />
N<br />
2<br />
N<br />
Me<br />
O<br />
N<br />
Me<br />
O<br />
H 2 N<br />
H 2 N<br />
H NH<br />
N<br />
2<br />
H 2 N<br />
H 2 N<br />
H 2 N<br />
H<br />
N<br />
O<br />
O<br />
HN<br />
HN<br />
O<br />
4<br />
H<br />
( )n N<br />
O<br />
5<br />
HN<br />
O<br />
HN<br />
( )n<br />
HN<br />
O<br />
Fig. 1. Examples <strong>of</strong> compounds containing polyamide and polyaromatic<br />
functional groups along <strong>the</strong> DNA recognizing chain.<br />
HN<br />
O<br />
O<br />
NH 2<br />
NH 2<br />
R<br />
COCl<br />
R<br />
23<br />
COCl<br />
R<br />
ClCO(CH 2 )nCOCl<br />
H 2 N<br />
R'<br />
H<br />
N<br />
N<br />
H<br />
NH 2<br />
R<br />
R<br />
R<br />
H<br />
N<br />
O<br />
O<br />
O<br />
N<br />
H<br />
N<br />
( )n<br />
6-20<br />
R'<br />
H<br />
N<br />
O<br />
H<br />
N<br />
N<br />
O<br />
O<br />
21,25 R'=Me<br />
22,23 R'=H<br />
O<br />
Pd / C<br />
H<br />
N<br />
N<br />
NH 2 NH 2 H<br />
O<br />
H 2 N<br />
24<br />
26-27<br />
Fig. 2. Syn<strong>the</strong>sis <strong>of</strong> compounds 6-27. (R values are reported on Table<br />
1.)<br />
R<br />
R<br />
R<br />
NH 2<br />
To study <strong>the</strong> influence <strong>of</strong> <strong>the</strong> length <strong>of</strong> <strong>the</strong> aliphatic chain<br />
on cytotoxic activity, we prepared compounds with a four<br />
methylene chain (12, 14, 16-18). It should be pointed out that<br />
compounds 13 (R = Cl) and 15 (R = I) were included due to<br />
<strong>the</strong> apparent tendency <strong>of</strong> halogens to present activity. In addition,<br />
compounds 19 (R = NHCOCH 3 ) and 20 (R = CN) were<br />
included in <strong>the</strong> study to investigate <strong>the</strong> effects <strong>of</strong> <strong>the</strong><br />
NHCOCH 3 and CN functional groups. In contrast to <strong>the</strong><br />
almost complete lack <strong>of</strong> activity shown by <strong>the</strong> first series (n =<br />
2), compound 12 (R = F) induced almost 100 % inhibition <strong>of</strong><br />
growth in K562 cell line and <strong>the</strong> functional groups OMe (16)<br />
and OH (17) were found to enhance cytotoxicity. The rest <strong>of</strong><br />
<strong>the</strong> compounds showed no activity.