Synthesis and In Silico studies of a novel 1,4-disubstituted-1,2,3-triazole-1,3-oxazole hybrid system

The development of new hybrid molecules that combine privileged heterocyclic structures remains a central challenge in medicinal chemistry. In this work, we report an efficient synthetic strategy for accessing novel 1,4-disubstituted-1,2,3-triazole-1,3-oxazole hybrids. The synthesis involves a two-step, three-sequence approach: a multicomponent reaction, subsequent oxidation, and the Van Leusen reaction. This operationally simple protocol proceeds under mild conditions and allows the rapid assembly of structurally diverse heterocyclic systems.
Three new hybrid molecules were synthesized and structurally characterized. To investigate their biological potential, we performed bioactivity prediction studies using cheminformatics tools. Polo-like kinase 3 (PLK3), a serine/threonine-protein kinase involved in cell cycle regulation and apoptosis, was identified as a potential molecular target. PLK3 is overexpressed in several types of cancer and is considered a promising target for the development of anticancer therapies.
Molecular docking simulations revealed that the synthesized compounds exhibit favorable interactions within the PLK3 binding site, including hydrogen bonding, π–π stacking, and hydrophobic contacts. The binding affinities and interaction profiles suggest a strong potential for these molecules as PLK3 inhibitors. These findings support further in vitro studies to evaluate their antiproliferative activity and validate their mechanism of action. Overall, this work highlights the potential of triazole–oxazole hybrids in the design of novel anticancer agents.