Synthesis and inverse virtual screening of new bi-cyclic structures towards cancer-relevant cellular targets

Abstract We report here synthetic approaches to access new classes of small molecules based on three heterocyclic scaffolds, i.e. 3,7-dihydropyrimido[4,5-d]pyridazine-4,8-dione, 1,8-naphthyridin-4(1 H )-one and 4H-pyrido[1,2-a]pyrimidin-4-one. The bi-cyclic structure 3,7-dihydropyrimido[4,5-d]pyridazine-4,8-dione is a heterocycle, described for the first time. In silico methodologies inverse virtual screening have been used preliminary analyse molecules, in order explore their potential as hits chemical biology investigations. Our computational study has conducted with 43 synthetically accessible towards 31 cellular proteins involved cancer pathogenesis. Binding energies were quantified using molecular docking calculations, allowing define relative affinities ligands targets. Through this methodology, 16 displayed effective interactions distinct within matrix. addition, 23 demonstrated high affinity at least one protein, reference co-crystallised ligand X-ray structure. evaluation ADME drug score selected also highlights that these series can serve sources lead candidates further optimisation biological studies.