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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Towards new C6-rigid S-DABO HIV-1 reverse transcriptase inhibitors: synthesis, biological investigation and molecular
Hai-Qiu Wu1, Zi-Hong Yan, Wen-Xue Chen
1Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China.
Abstract:
A series of C6-rigid S-DABO analogs characterized by a substituted benzoyl group at C6 position of the pyrimidine ring has been synthesized and biological evaluation as NNRTIs against wild-type HIV-1 strain IIIB, double RT mutant (K103N+Y181C) strain RES056 as well as HIV-2 strain ROD in MT-4 cell cultures. Most of the compounds exhibited moderate antiviral activities. Among them, compound 7q displayed the highest anti-HIV-1 activity with an EC50 value of 0.26μM and a selectivity index (SI) of 541. The preliminary structure-activity relationship (SAR) of these new S-DABOs was investigated, the target RT was confirmed and docking study was performed.
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