title: Antineoplastic activity of conjugates of lipids and 1-beta-D-arabinofuranosylcytosine.
abstract: Five different lipid conjugates of 1-beta-D-arabinofuranosylcytosine (ARA-C) were tested in comparison with ARA-C, the ether lipid ET-18-OCH3 (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) and their equimolar mixtures. The compounds were tested in vitro for cytotoxicity in the trypan blue dye exclusion test with cells from six different leukemias, one glioblastoma and two bronchogenic carcinomas of human origin. The compounds were given in vivo to assess their therapeutic activity against 3-Lewis lung carcinoma (3-LL) of syngeneic C57Bl6 mice. Although some of the conjugates have shown cytotoxic activity in vitro against the cell samples tested, they have not revealed higher cytotoxicity than ET-18-OCH3, ARA-C or their equimolar mixtures. In these experiments, ARA-CDP-D,L-MBA was the conjugates significantly inhibited tumor growth and also increased survival of C57Bl6 mice with intraperitoneally (ip) implanted 3-LL. In these experiments, ARA-CDP-D,L-PTBA, ARA-CDP-D,L-PBA, ARA-CDP-L-dipalmitin and ARA-CDP-D,L-PCA were more active than either the parent compounds ARA-C and ET-18-OCH3 alone or their equimolar mixtures. Furthermore, when the conjugates were injected as adjuvant chemotherapy shortly after the surgical removal of the primary 3-LL, they inhibited the metastasis of 3-LL to the lungs of the animals, demonstrated by an increase of the survival time and the number of surviving animals. The mode of action of these new antineoplastic compounds still is speculative.
authors.affiliation: Department of Medicine I, Technische Universitaet, Munich, Federal Republic of Germany.
authors.forename: W E
authors.initials: WE
authors.lastname: Berdel
authors.forename: S
authors.initials: S
authors.lastname: Danhauser
authors.forename: H D
authors.initials: HD
authors.lastname: Schick
authors.forename: C I
authors.initials: CI
authors.lastname: Hong
authors.forename: C R
authors.initials: CR
authors.lastname: West
authors.forename: M
authors.initials: M
authors.lastname: Fromm
authors.forename: U
authors.initials: U
authors.lastname: Fink
authors.forename: A
authors.initials: A
authors.lastname: Reichert
authors.forename: J
authors.initials: J
authors.lastname: Rastetter
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000378:metabolism / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008968:Molecular Conformation; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D010742:Phospholipid Ethers / Q000378:metabolism / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; D003561:Cytarabine