Synthesis, Antitumor, Antitrypanosomal And Antileishmanial Activities Of Benzo[4,5]canthin-6-ones Bearing The N′-(substituted Benzylidene)- Carbohydrazide And N-alkylcarboxamide Groups At C-2

A series of novel benzo[4,5]canthin-6-ones, bearing the N′-(substituted benzylidene)-carbohydrazide (11a-e) and N-alkylcarboxamide (13a-g) moieties at position-2, were synthesized and screened for their in vitro antitumor activity, against seven human cancer cell lines, and for antitrypanosomal and antileishmanial activities against Trypanosoma cruzi and Leishmania amazonensis. The results indicated that N-methylpiperazyl- 6-oxobenzo[4,5]canthine-2-carboxamide (13f) displayed potent antitumor activity with IC50 values in the range of 1.15-8.46 μM for all cell lines tested. Compounds 13f and 13g bearing an N-methylpiperazylcarboxamide and N-morpholylcarboxamide at C-2, respectively, showed potent activities towards both Trypanosoma cruzi and Leishmania amazonensis parasites, with IC 50 in the range of 0.4 to 16.70 μM. © 2012 The Pharmaceutical Society of Japan.601113721379De Souza Almeida, E.S., Filho, V.C., Niero, R., Clasen, B.K., Balogun, S.O., De Oliveira Martins, D.T., (2011) J. Ethnopharmacol., 134, pp. 630-636Jiao, W.H., Gao, H., Zhao, F., Lin, H.W., Pan, Y.M., Zhou, G.X., Yao, X.S., (2011) Chem. Pharm. Bull., 59, pp. 359-364Hsieh, P.W., Chang, F.R., Lee, K.H., Hwang, T.L., Chang, S.M., Wu, Y.C., (2004) J. Nat. Prod., 67, pp. 1175-1177Ferreira, M.E., Cebrián-Torrejón, G., Corrales, A.S., Vera De Bilbao, N., Rolón, M., Gomez, C.V., Leblanc, K., Fournet, A., (2011) J. Ethnopharmacol., 133, pp. 986-993Ferreira, M.E., Rojas De Arias, A., Torres De Ortiz, S., Inchausti, A., Nakayama, H., Thouvenel, C., Hocquemiller, R., Fournet, A., (2002) J. Ethnopharmacol., 80, pp. 199-202Soriano-Agatón, F., Lagoutte, D., Poupon, E., Roblot, F., Fournet, A., Gantier, J.C., Hocquemiller, R., (2005) J. Nat. Prod., 68, pp. 1581-1587Fournet, A.R.F., Lagoutte, D., Poupon, E., Soriano-Agaton, F., (2007), Pat. WO2007110500-A1, FR2899229-A1, EP1998770-A1, WO2007110500-A8, CN101448499-A, IN200808917-P1, EP1998770-B1, DE602007005992-EAmmirante, M., Di Giacomo, R., De Martino, L., Rosati, A., Festa, M., Gentilella, A., Pascale, M.C., De Feo, V., (2006) Cancer Res., 66, pp. 4385-4393Kuo, P.C., Shi, L.S., Damu, A.G., Su, C.R., Huang, C.H., Ke, C.H., Wu, J.B., Wu, T.S., (2003) J. Nat. Prod., 66, pp. 1324-1327Miyake, K., Tezuka, Y., Awale, S., Li, F., Kadota, S., (2010) Nat. Prod. Commun., 5, pp. 17-22Jiang, M.X., Zhou, Y.J., (2008) J. Asian Nat. Prod. Res., 10, pp. 1009-1012Peduto, A., More, V., De Caprariis, P., Festa, M., Capasso, A., Piacente, S., De Martino, L., Filosa, R., (2011) Mini Rev. Med. Chem., 11, pp. 486-491Barbosa, V.A., Formagio, A.S., Savariz, F.C., Foglio, M.A., Spindola, H.M., De Carvalho, J.E., Meyer, E., Sarragiotto, M.H., (2011) Bioorg. Med. Chem., 19, pp. 6400-6408Tonin, L.T.D., Barbosa, V.A., Bocca, C.C., Ramos, E.R.F., Nakamura, C.V., Da Costa, W.F., Basso, E.A., Sarragiotto, M.H., (2009) Eur. J. Med. Chem., 44, pp. 1745-1750Valdez, R.H., Tonin, L.T.D., Ueda-Nakamura, T., Dias Filho, B.P., Morgado-Diaz, J.A., Sarragiotto, M.H., Nakamura, C.V., (2009) Acta Trop., 110, pp. 7-14Tonin, L.T.D., Panice, M.R., Nakamura, C.V., Rocha, K.J.P., Dos Santos, A.O., Ueda-Nakamura, T., Da Costa, W.F., Sarragiotto, M.H., (2010) Biomed. Pharmacother., 64, pp. 386-389Pedroso, R.B., Tonin, L.T.D., Ueda-Nakamura, T., Dias Filho, B.P., Sarragiotto, M.H., Nakamura, C.V., (2011) Ann. Trop. Med. Parasitol., 105, pp. 549-557Cao, R., Peng, W., Wang, Z., Xu, A., (2007) Curr. Med. Chem., 14, pp. 479-500Gohil, V.M., Brahmbhatt, K.G., Loiseau, P.M., Bhutani, K.K., (2012) Bioorg. Med. Chem. Lett., 22, pp. 3905-3907Rivas, P., Cassels, B.K., Morello, A., Repetto, Y., (1999) Comp. Biochem. Physiol. C Pharmacol. Toxicol. Endocrinol., 122, pp. 27-31Ferreira, M.E., Nakayama, H., De Arias, A.R., Schinini, A., De Bilbao, N.V., Serna, E., Lagoutte, D., Fournet, A., (2007) J. Ethnopharmacol., 109, pp. 258-263Di Giorgio, C., Delmas, F., Ollivier, E., Elias, R., Balansard, G., Timon-David, P., (2004) Exp. Parasitol., 106, pp. 67-74Monks, A., Scudiero, D., Skehan, P., Shoemaker, R., Paull, K., Vistica, D., Hose, C., Boyd, M., (1991) J. Natl. Cancer Inst., 83, pp. 757-76

Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials (vol 134, pg 3547, 2011)

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