Synthesis and crystal structures of cancer cell differentiation inducers

Four effective differentiation inducers, the derivatives of HMBA, N, N, N', N' - tetracetylhexamethylenediamine, N, N' - hexamethylenebis (3 - pyridin ecarboxamide), 4, 4' - (hexane - 1, 6 - diyl)bis(piperazine - 2, 6 - dione) and 3, 3' - (hexane - 1, 6 - diyl) bis (5, 5 - dimethylhydantoin), have be en synthesized and identified by MS, NMR, IR and elemental analysis. The sy nthetic methods and routes have been optimized. The anticancer activity of 4, 4' - (hexane - 1, 6 - diyl) bis (piperazine - 2, 6 dione) against human erythroleukemia K562 cells was tested and its potency is ten times greater than ICRF 154[4, 4' - (ethane - 1, 2 - diyl) bis ( piperazine - 2, 6 - dion e) I. The structure of compound IV was determined by single crystal X - ray diffraction and compared with compounds I, II, III. In the structures of t hese compounds, the hexamethylene chain is fully extended, which can increa se the flexibility of the molecule. There are hydrogen bonds in compounds I I, M, IV. It is found that the hydrogen bonds and the ring structure of the functional groups can influence the activity of the compounds.