4078
L. Gupta et al. / Bioorg. Med. Chem. Lett. 17 (2007) 4075–4079
Table 2. Antileishmanial in vitro activity against luciferase–amastigote
system
6. Mcgregor, A. Lancet 1998, 351, 575.
7. Soto, J.; Arana, B. A.; Toledo, J.; Rizzo, N.; Vega, J. C.;
Diaz, A.; Luz, M.; Gutierre-Arboleda, M.; Berman, J. D.;
Junge, K.; Engel, J.; Sindermann, H. Clin. Infect. Dis.
2004, 38, 1266.
8. Prasad, R.; Kumar, R.; Jaiswal, B. P.; Singh, U. K. Indian
J. Pediatr. 2004, 71, 143.
9. Sangraula, H.; Sharma, K. K.; Rijal, S.; Koirala, S.
J. Assoc. Physians India 2003, 51, 686.
10. Carvalho, P. B.; Arribas, M. A. G.; Ferreira, E. I. Braz.
J. Pharm. Sci. 2000, 36, 69.
Compound
% inhibition (at 10 lg/ml)
7
8
97.72
75.06
59.06
97.78
TCL
78.06
NI
9
10
12
13
17
11. Akendengue, B.; Ngon-Milama, E.; Laurens, A.; Hoc-
quemiller, R. Parasite 1999, 6, 3.
TCL, total cell loss; NI, no inhibition.
12. Fournet, A.; Munoz, V. Curr. Top. Med. Chem. 2002, 2,
1215.
13. Camacho, M. R.; Croft, S. L.; Phillipson, J. D. Curr. Opin.
Anti-Infect. Investig. Drugs 2000, 2, 47.
14. Kobayashi, J.; Murayama, T.; Ishibashi, M.; Kosuge, S.;
Takamatsu, M.; Ohizumi, Y.; Kobayashi, H.; Ohta, T.;
Nozoe, S.; Sasaki, T. Tetrahedron 1990, 23, 7699.
15. (a) Weyand, M.; Schlichting, I. Biochemistry 1999, 38,
16469; (b) Huber, U.; Moore, R. E.; Patterson, G. M. L.
J. Nat. Prod. 1998, 61, 1304.
16. Skibo, E. B.; Xing, C.; Dorr, R. T. J. Med. Chem. 2001,
44, 3545.
17. Mewshaw, R. E.; Webb, M. B.; Marquis, K. L.; McGaug-
hey, G. B.; Shi, X.; Wasik, T.; Scerni, R.; Brennan, J. A.;
Andree, T. H. J. Med. Chem. 1999, 42, 2007.
18. Boyd, R. M.; McKee, C. T.; Pannell, K. L.; Bokesch, R.
H. Tetrahedron Lett. 2000, 41, 6305.
19. Bacher, G.; Nickel, B.; Emig, P.; Vanhoefer, U.; Seeber,
S.; Shandra, A.; Klenner, T. B.; Beckers, T. Cancer Res.
2001, 61, 392.
amastigote. Whereas compound (17) showed ꢀ99%
inhibition in promastigotes but no inhibition against
amastigote. Compounds (15) and (16) showed 78%
and ꢀ69% inhibition against promastigotes. It again
strengthens the fact that electron donating group pres-
ent either in indole ring or phenyl ring enhances the
activity. Compound (15) having two methoxy groups
present in the phenyl ring showed higher percentage of
inhibition as compared to (16), where only one methoxy
group attached to the phenyl ring. Rest of the com-
pounds (18–22) exhibit low percentage of inhibition in
promastigotes at a concentration of 10 lg/ml. The re-
sults prove that 8,9-dihydrocoscinamide B (7) and its
analogues (8–11) exhibited a better correlation of activ-
ity to indolylglyoxylamide derivatives (12–22). Compar-
atively inhibited activity of indolylglyoxylamide
derivatives may be attributed to the presence of one in-
dole ring.
20. (a) Sunduru, N.; Agarwal, A.; Katiyar, S. B.; Nishi;
Goyal, N.; Gupta, S.; Chauhan, P. M. S. Bioorg. Med.
Chem. 2006, 14, 7706; (b) Katiyar, S. B.; Srivastava, K.;
Puri, S. K.; Chauhan, P. M. S. Bioorg. Med. Chem. Lett.
2005, 15, 4957; (c) Kumar, A.; Katiyar, S. B.; Gupta, S.;
Chauhan, P. M. S. Eur. J. Med. Chem. 2006, 41, 106; (d)
Agarwal, A.; Srivastava, K.; Puri, S. K.; Chauhan, P. M.
S. Bioorg. Med. Chem. 2005, 13, 4645; (e) Agarwal, A.;
Ramesh; Ashutosh; Goyal, N.; Chauhan, P. M. S.; Gupta,
S. Bioorg. Med. Chem. 2005, 13, 6678; (f) Agarwal, A.;
Srivastava, K.; Puri, S. K.; Sinha, S.; Chauhan, P. M. S.
Bioorg. Med. Chem. Lett. 2005, 15, 5218; (g) Agarwal, A.;
Srivastava, K.; Puri, S. K.; Chauhan, P. M. S. Bioorg.
Med. Chem. 2005, 13, 6226; (h) Agarwal, A.; Srivastava,
K.; Puri, S. K.; Chauhan, P. M. S. Bioorg. Med. Chem.
Lett. 2005, 15, 531; (i) Agarwal, A.; Srivastava, K.; Puri, S.
K.; Chauhan, P. M. S. Bioorg. Med. Chem. Lett. 2005, 15,
1881; (j) Agarwal, A.; Srivastava, K.; Puri, S. K.;
Chauhan, P. M. S. Bioorg. Med. Chem. Lett. 2005, 15,
3130; (k) Agarwal, A.; Srivastava, K.; Puri, S. K.;
Chauhan, P. M. S. Bioorg. Med. Chem. Lett. 2005, 15,
3133; (l) Srivastava, S.; Tiwari, S.; Chauhan, P. M. S.;
Puri, S. K.; Bhaduri, A. P.; Pandey, V. C. Bioorg. Med.
Chem. Lett. 1999, 9, 653; (m) Srivastava, S.; Tiwari, S.;
Srivastava, S. K.; Chauhan, P. M. S.; Bhaduri, A. P.;
Pandey, V. C. Bioorg. Med. Chem. Lett. 1997, 7,
2741.
Leishmania occurs in third world countries. Prescribed
treatments are antimonials and benzamidines, known
for high toxicity. This necessitates development of safer
and more chemotherapeutic agents for treatment. 8,9-
dihydrocoscinamide B and its analogues have shown
promising in vitro activity, needing the concentrated
attention and perseverance of the scientific community
so that this lead compound may ultimately be developed
as very useful drug for the future benefits of mankind.
Acknowledgment
L.G. and A.T. thank University Grant Commission
(India) for providing financial support. We are also thank-
ful to S.A.I.F. Division, CDRI, Lucknow, for providing
spectroscopic data. CDRI communication No. 7152.
References and notes
1. (a) Desjeux, P. Trans. R. Soc. Trop. Med. Hyg. 2001, 95,
239; (b) Tropical Disease Research: Progress 1999–2000;
World Health Organization: Geneva, 2001.
2. (a) Olliaro, P. L.; Bryceson, A. D. M. Parasitol. Today
1993, 9, 323; (b) Werbovetz, K. A. Curr. Med. Chem. 2000,
7, 835.
3. Goldsmith, D. R.; Perry, C. M. Drugs 2004, 64, 1905.
4. Reithinger, R. Emerg. Infect. Dis. 2003, 9, 727.
5. Raht, S.; Trivellin, A.; Imbrunito, T. R.; Tomazela, D. M.;
Jesus, M. N.; Marzal, P. C.; Junior, H. F. A.; Tempone,
A. G. Estadoda Arte. Quim. Nova 2003, 26, 550.
21. (a) Mantyla, A.; Garnier, T.; Rautio, J.; Nevalainen, T.;
Vepsalainen, J.; Koskinen, A.; Croft, S. L.; Jarvinen, T.
J. Med. Chem. 2004, 47, 188; (b) Mantyla, A.; Rautio, J.;
Nevalainen, T.; Vepsalainen, J.; Juvonen, R.; Kendrick,
H.; Garnier, T.; Croft, S. L.; Jarvinen, T. Bioorg. Med.
Chem. 2004, 12, 3497; (c) Ashutosh; Gupta, S.; Ramesh;
Sundar, S.; Goyal, N. Antimicrob. Agents Chemother.
2005, 49, 3776.
22. Dembitsky, V. M. Russ. J. Bioorg. Chem. 2002, 28, 170.