A Review on Medicinal Chemistry and Biological Activity of Dihydropyrimidinones Against HIV

Dihydropyrimidinones (DHPMs), also referred to as pyrimidinones, are privileged structures widely employed in the search for new compounds capable of inhibiting HIV replication. This core is found in natural alkaloids isolated from marine sponge species, which are known to inhibit the binding of the viral surface protein gp120 to the CD4 receptor of target cells. In addition, DHPMs exhibit a close structural relationship with nucleic acids, macromolecules that constitute the genetic material of both living organisms and viruses. Furthermore, the DHPM nucleus is present in several important anti-HIV drugs that inhibit reverse transcriptase and integrase enzymes, indicating that the use of these privileged structures represents a faster and more promising approach for the development of novel HIV inhibitors. In this review, we provide an overview of DHPM-based compounds as potential future trends in AIDS treatment, with a focus on studies published over the last 10 years. Overall, our analysis indicates that compounds containing the DHPM core generally display high potency against multiple HIV targets and may overcome antiviral resistance, reinforcing the relevance of this pharmacophoric fragment for the development of effective and innovative antiretroviral therapies.