Design, Synthesis, Docking Studies, and Biological Evaluation of Novel 2-Hydroxyacetophenone Derivatives as Anti-HIV-1 Agents.

BACKGROUND

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.

OBJECTIVE

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

METHODS

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).

RESULTS

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.

CONCLUSION

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