The pharmaceutical industry is currently experiencing increasing demand for small-molecule drugs. However, a significant portion of the raw materials used in drug production are fossil-based, originating from crude oil. This reliance on non-renewable resources presents major challenges, particularly in the context of global environmental crises such as climate change, greenhouse gas emissions, and dwindling oil reserves.
In response, the shift toward renewable feedstocks and the development of sustainable technologies have become key priorities in scientific research. Among renewable resources, biomass is particularly promising due to its rapid replenishment rate and virtually unlimited supply. One of the most valuable organic compounds derived from biomass is 5-hydroxymethylfurfural (HMF).
The primary objective of this study was to investigate HMF's reactivity as a carbonyl component in the Passerini multicomponent reaction ( P-3CR ), with the aim of generating novel bioactive molecules. First, reaction conditions were optimized using a model system. Next, a chemolibrary of α-acyloxy carboxamides was synthesized. Finally, the compounds underwent preliminary biological evaluation for antiproliferative activity in cell lines relevant to chronic non-communicable diseases (particularly cancer) to assess their therapeutic potential. Additionally, a structure-activity relationship (SAR) analysis was conducted to identify how structural modifications influence bioactivity.