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,druglikeness and in silico ADME/Tox studies were carried out using free server tools.The heterofused hybrids 3-aryl-thiazolo[3,4-a]pyrazine-5,8-diones 3a-o were obtained in moderate to good yields(30-80%)and with high diastereomeric ratio.Notably,hybrids 3g-j showed good cytotoxic effect on Hep-G2 cancer cells IC_(50)(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 were cytotoxic on B16F10 melanoma cancer cells IC_(50)(20.9±5.3 μM,30.0±6.4 μM).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.