Antitumor agents. 207. Design, synthesis, and biological testing of 4beta-anilino-2-fluoro-4'-demethylpodophyllotoxin analogues as cytotoxic and antiviral agents.
2-Fluoropodophyllotoxin (11) and several 4beta-anilino-2-fluoro-4'-O-demethyl analogues were synthesized and evaluated in both antineoplastic and antiviral assays. These compounds were moderately active against some cancer cell lines, but they were less active than the corresponding nonfluorinated analogues. Compound 11 exhibited the best activity against KB carcinoma with a GI(50) of approximately 30 nM. Most compounds exhibited moderate activity against HCMV with ID(50) and ID(90) values in the range of 1 microM and 4 microM, respectively. Both 9 and 11 showed an unusual 10-fold selectivity for HSV-2 compared to HSV-1.
VanVliet
D S
DS
Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599-7360, USA.
Tachibana
Y
Y
Bastow
K F
KF
Huang
E S
ES
Lee
K H
KH
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D009693:Nucleic Acid Hybridization; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014709:Vero Cells
C425782:2-fluoropodophyllotoxin; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004247:DNA; D011034:Podophyllotoxin