Synthesis and anticancer activity of (RS)-9-(2,3-dihydro-1,4-benzoxaheteroin-2-ylmethyl)-9H-purines.

Abstract Herein are reported the synthesis and anticancer activity against the human breast cancer cell line MCF-7 of a series of substituted ( RS )-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9 H -purine derivatives and ( RS )-9-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-9 H -purine derivatives. When the Mitsunobu reaction was carried out between ( RS )-2,3-dihydro-1,4-benzoxathiin-3-methanol and the heterocyclic bases 6-chloro-, 2,6-dichloro, and 6-bromo-purines under microwave-assisted conditions, a formal 1,4-sulfur migration takes place through two consecutive oxyranium and episulfonium rings, giving rise to the corresponding ( RS )-9-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)-9 H -purine derivatives, previously reported by us. The most active compound ( RS )-2,6-dichloro-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9 H -purine shows an IC 50  = 2.75 ± 0.02 μM. When the cancerous cells were treated with this compound, a significant increase of apoptotic cells (70.08 ± 0.33%) was obtained in relation to the control ones. The induction of the G 2 /M cell cycle arrest and apoptosis by the three most active compounds is associated with increased phosphorylation of eIF2α in human breast cancer cells.