Synthesis, docking and evaluation of novel fused pyrimidine compounds as possible lead compounds with antibacterial and antitumor activities

•Chemoselective routes to new imidazo[1,2-a]pyrimidine derivatives, or regioisomeric hydrazonamide adducts.•Heterocyclic product outcome shown to be dictated by aromatic substituents in predictable manner.•Several compounds identified showing MIC values against gram+ve/–ve bacteria at sub-0.5 ug / mL.•Screening against HeLa cells identified a new imidazo[1,2-a]pyrimidine compound which an in silico target fishing analysis and modelling suggests could be targeting one or more of Tankyrase-2 (Tank-2), Cyclin-dependent kinase (CDK2) and Epidermal growth factor tyrosine kinase receptor (EGFR). Reaction of a series of hydrazonoyl chlorides with substituted aminopyrimidines afforded good selectivity in most cases leading either to formation of new imidazo[1,2-a]pyrimidine derivatives, or regioisomeric hydrazonamide adducts. The compounds were evaluated for antibacterial and anticancer activities. Screening against E. Coli, P. aeruginosa, S. aureus, S. epidermidis, B. subtilis and K. rhizophila did identify several different compound types with MIC of 0.1-0.4 mg/mL. Anticancer evaluation against a HeLa cell line identified one imidazo[1,2-a]pyrimidine lead. An in silico target fishing analysis suggest three possible high value protein targets, Tankyrase-2 (Tank-2), Cyclin-dependent kinase (CDK2) and Epidermal growth factor tyrosine kinase receptor (EGFR), with modelling fit against co-crystallized known ligands. This provides a new structural family lead for further investigation of molecular targets and potential SAR activity development. [Display omitted]