Design, synthesis, and molecular docking of dihydropyrimidine-schiff base derivatives as potential EGFR/Bcl-2 inhibitor candidates

Background Cancer remains a major global health challenge characterized by uncontrolled cell proliferation, necessitating the development of novel targeted therapeutic agents with improved predicted interaction potential and selectivity. Objectives This study aimed to design, synthesize, and computationally evaluate dihydropyrimidine-Schiff base derivatives for their predicted interactions with EGFR and Bcl-2 proteins. Methods A series of ten novel derivatives (3a-3j) were synthesized using a microwave-assisted one-pot multicomponent reaction and characterized by ¹H NMR, ¹ ³C NMR, and HR-MS techniques. Molecular docking studies were performed against EGFR and Bcl-2 targets, followed by an examination of the structure-activity connection and an in-silico assessment of binding interactions. Results Docking studies suggested moderate docking affinity of the synthesized compounds toward EGFR and Bcl-2 targets, with docking scores ranging from −5.0 to −7.0 kcal/mol. Among the tested compounds, compound 3 h showed the best docking contacts, which may be attributed to favourable interactions with key active site residues and the presence of hydroxyl substituents. Structure-activity relationship analysis suggested that substituent variation influences docking-predicted interactions with the target proteins. Conclusions The synthesized dihydropyrimidine derivatives demonstrated moderate docking-predicted interactions and may serve as preliminary docking hits for further experimental investigation for further optimization. However, these findings are preliminary computational observations and require experimental validation to further assess their biological relevance and molecular interactions.