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

摘要

A new series of heterofused thiazolo/pyrazinedione hybrids were designed, synthetized and their cytotoxicity potential was evaluated against different cancer cell lines. Besides, drug-likeness and in silico ADME/Tox studies were carried out using free server tools. The heterofused hybrids 3-aryl-thiazolo3,4-apyrazine-5,8-diones 3 a-o were obtained in moderate to good yields (30-80 ) and with high diastereomeric ratio. Notably, hybrids 3 g-j showed good cytotoxic effect on Hep-G2 cancer cells IC50 (28.6 +/- 4.9 mu M, 54.2 +/- 15.4 mu M, 95.2 +/- 1.9 mu M, 68.6 +/- 1.6 mu M) respectively, while compounds 3 l-m were cytotoxic on B16F10 melanoma cancer cells IC50 (20.9 +/- 5.3 mu M, 30.0 +/- 6.4 mu M). Furthermore, the new compounds were relatively non-toxic on Vero cells. In silico drug-likeness and ADME/Tox studies suggest optimal pharmacokinetic profile for all hybrids. Altogether, these new heterofused hybrids could be considered as promising scaffolds in cancer chemotherapy.