Synthesis of Dihydropyrimidinone (DHPM) Derivatives through a Multicomponent Reaction (MCR) and Their Biological Activity

The spread of incurable diseases, especially infectious diseases caused by antibiotic-resistant bacteria and certain cancers, has become a serious public health concern. Consequently, the search for potent drug scaffolds has played an essential role in drug lead discovery. The multicomponent reaction (MCR) offers a novel method for efficient synthesis. It is rapidly evolving and is important for the discovery of novel molecules. We synthesized four dihydropyrimidinone (DHPM) derivatives with the one-pot MCR method, obtaining compounds ۱-۴. According to the NMR spectra analyses, compound ۳ is a new derivative. In this experiment, we optimized the pH of the process. Based on the results, ۱-۴ had yields of ۶۶.۶, ۷۲.۹, ۳۵.۹, and ۶۹.۰%, respectively, at a pH of ۴. In contrast, all yields significantly rose by ۷۹.۴, ۹۱.۹, ۸۱.۷, and ۸۴.۰% at pH ۵. A pH of ۵ was therefore advantageous for getting a high yield from these reactions. Compound ۱ showed a significant inhibition against E. coli with an MIC value of ۱۲.۵ µg/mL with moderate activity against the breast cancer cell lines T۴۷D and ۴T۱. Compound ۳ was the most potent against S. aureus, with an MIC value of ۲۵ µg/mL.

Keywords:

Dihydropyrimidinone derivatives , Bioactivity , E. coli , Staphylococcus aureus , T۴۷D and ۴T۱ cell lines