期刊
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
卷 20, 期 8, 页码 1533-1553出版社
MARCEL DEKKER INC
DOI: 10.1081/NCN-100105246
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A group of unnatural 1-(2-deoxy-beta -D-ribofuranosyl)isocarbostyrils having a variety of C-7 substituents [H, 4,7-(NO2)(2), I, CF3, CN, (E)-CH=CH-I, -C drop CH, -C dropC-I, -C dropC-Br, -C dropC-Me], designed as nucleoside mimics, were synthesized for evaluation as anticancer and antiviral agents. This class of compounds exhibited weak cytotoxicity in a MTT assay (CC50 = 10(-3) to 10(-5) M range) with the 4,7-dinitro derivative being the most cytotoxic, relative to thymidine (CC50=10(-3) to 10(-5) M range), against a variety of cancer cell lines. The 4,7-dinitro, 7-I and 7-C drop CH compounds exhibited similar cytotoxicity against nontransfected (KBALB, 143B), and HSV-1 TK+ gene transfected (KBALB-STK, 143B-LTK) cancer cell lines possessing the herpes simplex virus type I (HSV-1) thymidine kinase gene (TK+). This observation indicates that these compounds are not substrates for HSV type-1 TK, and are therefore unlikely to be useful in gene therapy based on the HSV gene therapy paradigm.
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