662
E. del Olmo et al. / Bioorg. Med. Chem. Lett. 12 (2002)659–662
brasiliensis (2903) strain could be noticed: >80% lysis
versus <70% lysis for the other two strains, at 10 mg/
mL. As it was appreciated for amino-alcohols and di-
esters, large groups at both amine ends are not
recommended for the activity (9b/9e) and similarly the
free acids are less potent than their corresponding esters
5. World Health Organization (OMS). Rapport sur la Sante´
dans le Monde; WHO: Geneve, 1998.
. Chakrabarti, G.; Basu, A.; Manna, P. P.; Mahato, S. B.;
Mandal, N. B.; Bandyopadhyay, S. J. Antimicrob. Chemother.
`
6
1
999, 43, 359.
. Gamage, S. A.; Figgit, D. P.; Wojcik, S. J.; Ralph, R. K.;
7
Ransijn, A.; Mauel, J.; Yardley, V.; Snowdon, D.; Croft, S. L.;
0 0
9c /9c and 9d /9d). However the most potent mono-
(
Denny, W. A. J. Med. Chem. 1997, 40, 2634.
8
substituted compound 9f is nearly as potent as the dis-
ubstituted 9d, perhaps due to the presence of the amide
group or to the longer separation between both fun-
tional groups. Disubstitued amines are more potent
than those monosubstituted (8b/8a, 9b/9a, 9d/9c),
excepting the Boc diester 8d.
. Khan, M. O.; Austin, S. E.; Chan, C.; Yin, H.; Marks, D.;
Vaghjiani, S. N.; Kendrick, H.; Yardley, V.; Croft, S. L.;
Douglas, K. T. J. Med. Chem. 2000, 43, 3148.
9. (a) Avila, J. L.; Polegre, M. A.; Avila, A.; Robins, R. K.
Comp. Biochem. Physiol. 1986, 83, 285. (b) Cottam, H. B.;
Petrie, C. R.; McKernan, P. A.; Goebel, R. J.; Dalley, N. K.;
Davidson, R. B.; Revankar, G. R. J. Med. Chem. 1984, 27,
1
1
1
1
119.
We have found, therefore, a new leishmanicidal mol-
ecular prototype, less toxic (data not shown) than the
reference drug Amphotericin B and displaying as
the main structural features a fatty 1,2-diamine with the
0. Aronov, A. M.; Gelb, M. H. Bioorg. Med. Chem. Lett.
998, 8, 3505.
1. Benbow, J. W.; Bernberg, E. L.; Korda, A.; Mead, J. R.
Antimicrob. Agents Chemother. 1998, 42, 339.
12. Mittra, B.; Saha, A.; Chowdhury, A. R.; Pal, C.; Mandal,
S.; Mukhopadhyay, S.; Bandyopadhyay, S.; Majunder, H. K.
Mol. Med. 2000, 6, 527.
1
-NH group disubstituted by small alkyl or alkoxy-
2
carbonylmethyl groups and with the NH2 group at
position 2 preferably free or protected.
1
3. (a) Kayser, O.; Kiderlen, A. F.; Laastsch, H.; Croft, S. L.
Acta Trop. 2000, 76, 131. (b) Cauchetier, E.; Paul, M.; Rivol-
let, D.; Fessi, H.; Astier, A.; Denian, M. Int. J. Parasitol. 2000,
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1
This work was supported by JCyL (Grant No SA25/
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Trop. Med. Hyg. 1987, 36, 288.
0
0B). This collaborative work was performed under the
auspices of the CYTED Program (Programa Ibero-
americano de Ciencia y Tecnologıa para el Desarrollo),
SubProgram X.
1
5. Croft, S. L.; Snowdon, D.; Yardley, V. J. Antimicrob.
Chemother. 1996, 38, 1041.
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