Synthesis, characterization, and biological assessment of riboflavin-theobromine derivatives for pediatric traumatic infection applications

The synthesis of novel theobromine and riboflavin derivatives was achieved through two distinct chemical pathways. Riboflavin derivative (2) was obtained by acetylating a tetrahydroxypentyl side chain, while theobromine derivative (7) was synthesized via a multistep reaction involving potassium hydroxide, phenylmethanamine, and N-benzyl-2-chloroacetamide. Both reactions proceeded under mild conditions and were characterized using ¹H-NMR, ¹³C-NMR, and mass spectrometry. In addition to chemical characterization, compounds 2 and 7 were evaluated for their potential impact on traumatic infection prognosis in children. Observational analysis of pediatric data identified Riboflavin (2), Theobromine (7), Vitamin B12, and Zn as significant factors influencing infection risk (P < 0.05). These associations were further validated through Mendelian Randomization (MR) analysis, suggesting a potential causal role. After adjusting for confounding variables, nutrient supplementation was found to improve infection prognosis. These findings highlight the therapeutic relevance of the synthesized compounds and provide a foundation for future biochemical and medicinal studies. KEY WORDS: Theobromine derivatives, Riboflavin derivatives, Acetylation, Potassium hydroxide, Post-traumatic infection, Mendelian randomization, Essential nutrient Bull. Chem. Soc. Ethiop. 2025, 39(10), 2027-2039. DOI: https://dx.doi.org/10.4314/bcse.v39i10.11