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

Abstract

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 GI₅₀ level (LogGI₅₀ is−6.40 to−4.02 for different cell lines, LogGI₅₀ 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 (LogGI₅₀=−6.40) and SR (LogGI₅₀=−6.06).

Keywords:

• 4-thioxo-2-thiazolidones
• thiopyrano[2,3-d]thiazole derivatives
• hetero-Diels-Alder reaction
• anticancer activity in-vitro
• 5-norbornene-2,3-dicarboxylic acid imides

Acknowledgements

We thank Dr. V.L. Narayanan from the Drug Synthesis and Chemistry Branch, National Cancer Institute, Bethesda, MD, USA, for in vitro evaluation of anticancer activity.