Influence of 1-β-d-Arabinofuranosylcytosine Conjugates of Lipids on the Growth and Metastasis of Lewis Lung Carcinoma
1988
Abstract Five different lipid conjugates of 1-β-d-arabinofuranosylcytosine (ara-C) were tested for their therapeutic activity on the growth and metastasis of Lewis lung carcinoma (3-LL). Among 1 ester-linked lipid conjugate (Ara-CDP-l-dipalmitin), 3 1- O -alkyl-lipid conjugates (ara-CDP-d,l-PBA, ara-CDP-d,l-PCA, ara-CDP-d,l-MBA) and a thioether-lipid conjugate (ara-CDP-d,l-PTBA) ara-CDP-d,l-PTBA, ara-CDP-d,l-PBA, and ara-CDP-l-dipalmitin produced the strongest tumor growth inhibition and increase of surviving animals in C 57 Bl 6 -mice bearing i.p.-implanted 3-LL. Furthermore these conjugates were superior to the parent compounds alone, or equimolar mixtures of the alkyllysophospholipid derivatives ET-18-OCH 3 and ara-C. Successful therapeutic regimen consisted of 80–100 mg conjugate/kg, given i.p. daily for five consecutive days. Similar regimen injected shortly after the surgical removal of the primary tumor as adjuvant chemotherapy inhiibited the metastasis of 3-LL to the lungs of the animals as demonstrated by an increase of survival time and the number of surviving animals.
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