A green one-pot synthetic protocol of hexahydropyrimido [4, 5-d] pyrimidin-4 (1 H)-one derivatives: molecular docking, ADMET, anticancer and antimicrobial studies

Abstract

Ten hexahydropyrimido[4,5-d]pyrimidine derivatives have been synthesized by using a green and time-efficient microwave method. The synthesized motifs were evaluated for their anticancer activity, antimicrobial activity, molecular docking, drug likeliness and ADMET studies. Comparatively, the hetero-aromatic pyrazole substituted compound 4a exhibited the highest anticancer activity [Mean growth percent: 35.57], while EDG [–N(CH3 ) 2 ] substituted compound 4i indicated very good activity [Mean growth percent: 60.92] against various cell lines. From the computational studies, Compound 4a passed the drug-likeness and ADME properties, fewer toxic properties, and potent inhibitory potential against the RIPK2 with significant binding affinity. In-silico molecular docking revealed that the compound 4a has significant binding energy (− 9.8 kcal/mol) and dissociation constant (0.54 μM) properties. Additionally, synthesized motifs were evaluated for antimicrobial activity by MIC referencing the standards. According to the SAR evaluations, the compounds 4f (4-NO 2 ), 4g (3-NO 2 ), and 4h (2-Cl) that include EWGs substituted aldehydes performed well as antimicrobials against selected bacterial and fungal strains. Thus, the synthesized pyrimido[4,5-d]pyrimidine with the heterocyclic and EWGs substituents could act as a potential candidate after further structural optimization for anticancer and antimicrobial drug discovery, respectively