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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
SAR and Lead Optimization of an HIV-1 Vif-APOBEC3G Axis Inhibitor
Idrees Mohammed1, Maloy K Parai1, Xinpeng Jiang1
1Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, California 92037 (USA).
Abstract:
We describe structure-activity relationship and optimization studies of RN-18, an HIV-1 Vif-APOBEC3G axis inhibitor. Targeted modifications of RN-18 ring-C, ring-B, ring-A, bridge A-B, and bridge B-C were performed to identify the crucial structural features, which generated new inhibitors with similar (4g and 4i) and improved (5, 8b, and 11) activities. Two potent water-soluble RN-18 analogues, 17 and 19, are also disclosed, and we describe the results of pharmacological studies with compound 19. The findings described here will be useful in the development of more potent Vif inhibitors and in the design of probes to identify the target protein of RN-18 and its analogues.
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