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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Anti-HIV diarylpyrimidine-quinolone hybrids and their mode of action
Tian-Qi Mao1, Qiu-Qin He2, Zheng-Yong Wan2
1Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China; Institute of Biomedical Science, Fudan University, Shanghai 200433, People's Republic of China.
Abstract:
A molecular hybridization approach is a powerful tool in the design of new molecules with improved affinity and efficacy. In this context, a series of diarylpyrimidine-quinolone hybrids were synthesized and evaluated against both wt HIV-1 and mutant viral strains. The most active hybrid 5a displayed an EC50 value of 0.28±0.07μM against HIV-1 IIIB. A couple of enzyme-based assays clearly pinpoint a RT-targeted mechanism of action. Docking studies revealed that these hybrids could be well located in the NNIBP of HIV-1 RT despite the bulky and polar properties of a quinolone 3-carboxylic acid moiety in the molecules.
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