Synthesis and antiproliferative activities of two new analogs of tetrazepinones

Based on the encouraging results, we report the multistep synthesis and the biologicalo results of two new analogs of tetrazepinones: the 3,5-dimethyl-6-phenyl-8-(trifluoromethyl-5,6-dihydropyrazo1o[3-4-f]1,2,35)tetrazepin-4(3H)-one and the 3-(2-chloroethyl)-5-methyl-6-phenyl-8-(trifluoromethyl-5,6-dihydropyrazo1o[3-4-f]1,2,35)tetrazepin-4(3H)-one. Both compounds showed a pro-apoptotic activity against HL60 and K562 resistant cell lines. Flow cytometry studies carried out 0n K562 cells allowed to establish that the methyl derivative induces G0-G1, phase arrest followed by apoptosis, whereas the chloroethyl derivative is a not phase-specific agent.