CRYSTAL AND SOLUTION-STATE CONFORMATIONS OF 2 TAXOIDS, TAXININE AND TAXININE-B

Crystal and solution state conformations of two taxoids, taxinine and taxinine B, inhibiting the drug transport by P-glycoprotein in multidr ug-resistant cells, were analyzed by X-ray crystallographic analysis a nd ROE experiments. This study demonstrated that in solid state, both taxinine and taxinine B took similar cage conformation in which A-ring and the cinnamoyl side chain at C-ring were specially very close to e ach other. These conformations were also observed in their solution co nformations deduced by ROE correlations in CDCl3, Monte Carlo simulati on using MM2 force field, and semiempirical molecular orbital calcula tion using PM3 method. (C) 1997 Elsevier Science Ltd.