Anti-AIDS agents. Part 61: Anti-HIV activity of new podophyllotoxin derivatives.
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.
Zhu
Xiao-Kang
XK
Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7360, USA.
Guan
Jian
J
Xiao
Zhiyan
Z
Cosentino
L Mark
LM
Lee
Kuo-Hsiung
KH
D000163:Acquired Immunodeficiency Syndrome; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents