title: Synthesis and evaluation of anti-tumor activities of N4 fatty acyl amino acid derivatives of 1-beta-arabinofuranosylcytosine.
abstract: 1-Beta-D-arabinofuranosylcytosine (Ara-C, Cytarabine) is one of the drugs used for acute nonlymphocytic leukemia (ANLL). However, the bioavailability of Ara-C is relatively low due to its low lipophilicity. In order to improve the lipophilicity and bioavailability of Ara-C, a series of N(4) derivatives of Ara-C, i.e., (fatty acid)-(amino acid)-Ara-C analogues, were prepared. The 15 derivatives synthesized were characterized by their melting points, optical rotations and partition coefficients. It was found that the Ara-C derivatives synthesized in this study were more lipophilic than Ara-C as determined by their partition coefficients. Their in vitro cytotoxicity and in vivo anti-tumor activity were determined and compared with that of Ara-C. It was found that the derivatives were more active than Ara-C in Hela cells, but not in HL-60 cells. The in vivo results showed that some of the derivatives were more effective than Ara-C in mice bearing S(180) tumor while others showed a decreased activity in comparison with Ara-C.
authors.affiliation: School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Boyang
authors.initials: B
authors.lastname: Liu
authors.forename: Chunying
authors.initials: C
authors.lastname: Cui
authors.forename: Wei
authors.initials: W
authors.lastname: Duan
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Shiqi
authors.initials: S
authors.lastname: Peng
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
authors.forename: Guohui
authors.initials: G
authors.lastname: Cui