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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-AIDS agents. Part 61: Anti-HIV activity of new podophyllotoxin derivatives
Xiao-Kang Zhu1, Jian Guan, Zhiyan Xiao
1Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7360, USA.
Abstract:
A series of novel podophyllotoxin derivatives containing structural modifications at C-4 (7-14), C-4' (16-17), and the methylenedioxy A-ring (23-28) was synthesized and tested for inhibition of HIV replication. Four of these compounds (25-28) were previously reported to show EC(50) values of <0.001 microg/mL and therapeutic index (TI) values >120. Three of the newly tested compounds (8, 12, and 20) showed good activity with EC(50) values of 0.012, <0.001, and 0.389 microg/mL and TI values of 19.1, >16, and 19.4, respectively. A comparison of the anti-HIV activity of these derivatives suggested that an opened A-ring with 6,7-dimethoxy substitution and a 4'-demethylated E ring enhanced anti-HIV activity.
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