MNDO STUDIES ON THE STRUCTURE OF ANTINEOPLASTON A10, GLUTARIMIDE AND PIPERIDINE

Molecular geometries, heats of formation and dipole moments were calculated for 3-acetylamino-2,6-piperidinedione (the derivative of Antineoplaston A10 antitumour drug), glutarimide and piperidine using the MNDO method. The results obtained have shown that the NH equatorial conformer of piperidine is more stable than the axial one by 0.52 kcal mol-1 and the ring geometries of the two conformers are slightly different, which is supported by the microwave data. Glutarimide molecule has a "half-chair" conformation and the atoms O-C-N(H)-C-O are approximately coplanar. The calculated molecular geometry of 3-acetylamino-2,6-piperidinedione is in very good agreement with the recently obtained X-ray crystal structure of synthetic Antineoplaston A10. It is concluded that significant flattening of the piperidinedione ring in Antineoplaston A10 and its structural resemblance with uracil and thymine enables the A10 molecules to intercalate between base pairs in a DNA helix.