New Heterofused Thiazolo/Pyrazinedione Hybrids as Promising Building Blocks for Anticancer Drug Development: Synthesis, Biological and Drug‐Likeness Evaluation

A new series of heterofused thiazolo/pyrazinedione hybridswere designed, synthetized and their cytotoxicity potential wasevaluated against different cancer cell lines. Besides, druglikenessand in silico ADME/Tox studies were carried out usingfree server tools. The heterofused hybrids 3-aryl-thiazolo[3,4-a]pyrazine-5,8-diones 3a–o were obtained in moderate togood yields (30–80%) and with high diastereomeric ratio.Notably, hybrids 3g–j showed good cytotoxic effect on Hep-G2cancer cells IC50 (28.6�4.9 μM, 54.2�15.4 μM, 95.2�1.9 μM,68.6�1.6 μM) respectively, while compounds 3l–m werecytotoxic on B16F10 melanoma cancer cells IC50 (20.9�5.3 μM,30.0�6.4 μM). Furthermore, the new compounds were relativelynon-toxic on Vero cells. In silico drug-likeness and ADME/Tox studies suggest optimal pharmacokinetic profile for allhybrids. Altogether, these new heterofused hybrids could beconsidered as promising scaffolds in cancer chemotherapy. Fil: Cala Gómez, Luis Javier. Universidad Industrial Santander; Colombia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Álvarez Santos, Marilyn R.. Universidad Industrial Santander; Colombia