Synthesis and anticancer activity of novel thiopyrano[2,3-d]thiazole-based compounds containing norbornane moiety

The series of 9,14-disubstituted 3,7-dithia-5,14-diazapentacyclo[9.5.1.0(2,10).0(4,8).0(12,16)]heptadecen-4(8)-triones- 6, 13, 15 were synthesized using hetero-Diels-Alder reactions starting from 4-thioxo-2-thiazolidinones and 5-norbornene-2,3-dicarboxylic acid imido-derivatives. Screening of anticancer activity in vitro yielded the most active compounds 5c, 5d, and 7b in micromolar concentrations at the GI(50) level (LogGI(50) is -6.40 to -4.02 for different cell lines, LogGI(50) mean graph midpoint varies from -4.67 to -4.05); moreover, compounds 5c and 5d have a distinctive selectivity against leukemia. The highest sensitivity to compound 5d showed leukemia cell lines CCRF-CEM (LogGI(50) = -6.40) and SR (LogGI(50) = -6.06).