Sustainable synthesis and comprehensive biological & computational evaluation of pyrimidine derivatives

Abstract The rising prevalence of multidrug-resistant pathogens and the global burden of cancer necessitate the development of new therapeutic agents using sustainable, innovative approaches. Pyrimidine derivatives have attracted considerable attention due to their diverse biological activities, including antimicrobial and anticancer properties. Despite numerous reports on their synthesis, a clear gap remains in the literature regarding green synthesis protocols that combine eco-friendly reaction conditions with comprehensive biological and computational evaluations. In this work, we report a sustainable synthesis of these compounds using both conventional and microwave-assisted methods. Furthermore, we provide detailed characterization and in vitro assessments of biological activity. Compounds 7c , 8c , and 10a showed promising results, while extensive computational studies (DFT, molecular docking, and MD simulations) were conducted to elucidate the structure–activity relationships. This integrated approach not only deepens understanding of the pharmacological potential of these compounds but also aligns with the principles of green chemistry, offering a promising pathway for future drug discovery.