Abstract
A molecular modeling study of two alkaloids, tubulosine and psychotrine, isolated from the sap of Pogonopus speciosus, and other related ipecac alkaloids, showed that these flexible alkaloids favor a nonplanar structure. The biologically active compounds had conformations with a similar angle between aromatic ring A, the nitrogen in ring B, and ring D. This angle was related to the biological activity reported for these compounds. Our results support the hypothesis of two different types of receptor interactions, one for the nonplanar compounds and another for the planar compounds.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ma, W.W, Anderson, J.L., McKenzie, A.T., Byrn, S.R. and McLaughlin, J.L., J. Nat. Prod., 53 (1990) 1009.
Meyer, B.N., Ferrigni, N.R., Putnam, J.E., Jacobsen, L.B., Nichols, D.E. and McLaughlin, J.L., Planta Med., 45 (1982) 31.
Ferrigni, N.A., Putnam, J.E., Anderson, B., Jacobsen, L.B., Nichols, D.E., Moore, D.S., McLaughlin, J.L., Powell, R.G. and Smith Jr., J.R., J. Nat. Prod., 45 (1982) 679.
Suffness, M. and Cordell, G.A., in Brossi A. (Ed) Antitumor Alkaloids, The Alkaloids, Vol. 25, Academic Press, Orlando, FL, 1985, pp. 48–55.
Gupta, R., Krepinsky, J.J. and Siminovitch, L., Mol. Pharmacol., 18 (1980) 136.
Quetin-Leclerck, J., Dupont, L., Wrigth, C.W., Phillipson, J.D., Warhurst, D.C. and Angenot, J., J. Pharm. Belg., 46 (1991) 85.
CAChe (Computer Aided Chemistry), version 3.5.1, Reference Manual, CAChe Scientific, Beaverton, OR, USA, 1993.
Allinger, N.L., J. Am. Chem. Soc., 108 (1977) 8153.
Billeter, M., Howard, A.E., Kuntz, L.D. and Kollman, P.A., J. Am. Chem. Soc., 110 (1988) 8385.
Cache Molecular Mechanics V.3.0 x settings: optimization by the Block Diagonal Newton Raphson Method; relaxation factor + 1.00; energy value tolerance = 0.001 kcal/mol. Included terms bond stretch, bond angle, dihedral improper torsion, van der Waals, electrostatic and hydrogen bonding, as augmented by CAChe Scientific.
Auffinger, P. and Wipff, G., J. Comput. Chem., 11 (1990) 19.
Brady, J.W., J. Am. Chem. Soc., 108 (1986) 815.
Nakano, T., Maillo, M.A., Cordero de Troconis, M. and Usubillaga, A., Nat. Prod. Lett., 6 (1995) 63.
Sanders, M., Honk, K.N., Wu, Y.D., Still, W.C., Lipton, M., Chang, G. and Guida, W.C., J. Am. Chem. Soc., 112 (1990) 1419.
Dölz, H., Vázquez, D. and Jiménez, A., Biochemistry, 21 (1982) 3181.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Troconis, M., Ma, W., Nichols, D.E. et al. Molecular modeling study of tubulosine and other related ipecac alkaloids. J Comput Aided Mol Des 12, 411–418 (1998). https://doi.org/10.1023/A:1008019720578
Issue Date:
DOI: https://doi.org/10.1023/A:1008019720578