Design, Synthesis, Docking Studies, and Biological Evaluation of Novel 2-Hydroxyacetophenone Derivatives as...

The persistence of HIV mutations and the existence of multidrug resistance have produced an opportunity for an array of innovative anti-HIV medicines with a variety of structures that target HIV key enzymes.

The goal of this work was to find a new class of anti-HIV drugs founded on HIV integrase inhibitor pharmacophores.

A novel class of 2-hydroxy acetophenone analogs featuring substituted benzamide or N-phenylthiourea groups was designed and synthesized based on the general pharmacophore of HIV-1 integrase inhibitors (INs).

Most of the synthesized analogs were found to be moderately active against the virus, with EC₅₀ values ranging from 40 to 140 μM. Additionally, it was found that most of the compounds presented no considerable cytotoxicity (CC₅₀ > 500 μΜ). The most potent compounds substituting with 4-fluorobenzamide (compound 7) and 4-methylbenzamide (compound 9) rings inhibited the HIV-1 replication by EC₅₀ values of 40 and 45 μΜ, respectively. Docking studies using the crystallographic data available for PFV IN indicated that the Mg²⁺ coordination might be the possible mechanism of the anti-viral activity.

Our findings proved that the synthesized analogs may suggest a very good basis for the development of new anti-HIV-1 agents.