1. Academic Validation
  2. Synthesis and evaluation of anti-tumor activities of N4 fatty acyl amino acid derivatives of 1-beta-arabinofuranosylcytosine

Synthesis and evaluation of anti-tumor activities of N4 fatty acyl amino acid derivatives of 1-beta-arabinofuranosylcytosine

  • Eur J Med Chem. 2009 Sep;44(9):3596-600. doi: 10.1016/j.ejmech.2009.02.028.
Boyang Liu 1 Chunying Cui Wei Duan Ming Zhao Shiqi Peng Lili Wang Hu Liu Guohui Cui
Affiliations

Affiliation

  • 1 School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China.
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.

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