Synthesis of halogen-substituted 3-deazaadenosine and 3-deazaguanosine analogues as potential antitumor/antiviral agents.
Various 2-halogen-substituted analogues (38, 39, 43 and 44), 3-halogen-substituted analogues (51 and 52), and 2',3'-dihalogen-substituted analogues (57-60) of 3-deazaadenosine and 3-halogen-substituted analogues (61 and 62) of 3-deazaguanosine have been synthesized as potential anticancer and/or antiviral agents. Among these compounds, 3-deaza-3-bromoguanosine (62) showed significant cytotoxicity against L1210, P388, CCRF-CEM and B16F10 cell lines in vitro, producing IC50 values of 3, 7, 9 and 7 microM, respectively. Several 3-deazaadenosine analogues (38, 51, 57 and 59) showed moderate to weak activity against hepatitis B virus.
Liu
M C
MC
Department of Pharmacology and Developmental Therapeutics Progam, Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520-8066, USA.
Luo
M Z
MZ
Mozdziesz
D E
DE
Lin
T S
TS
Dutschman
G E
GE
Gullen
E A
EA
Cheng
Y C
YC
Sartorelli
A C
AC
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001671:Biochemistry / Q000379:methods; D004354:Drug Screening Assays, Antitumor; D006151:Guanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects; D006219:Halogens / Q000737:chemistry; D006515:Hepatitis B virus / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007939:Leukemia L1210; D008826:Microbial Sensitivity Tests; D014407:Tumor Cells, Cultured
C458799:3-deaza-3-bromoguanosine; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D006219:Halogens; D006151:Guanosine; C010568:3-deazaguanosine