An in vitro assessment of the antineoplastic potential of 2H-1,3-oxazine-2,6(3H)-dione (3-oxauracil), a novel pyrimidine

Invest New Drugs. 1997;15(4):289-93. doi: 10.1023/a:1005962224801.

Abstract

The pyrimidine (uracil) analogue 3-oxauracil (OU) previously had been shown to completely inhibit the growth of E. coli B and decrease by 96% the replication of herpes simplex virus type 2 when present in the culture fluid at a concentration of 10(2) microM. Limited in vivo studies in mice demonstrated antiviral effects without significant toxicity when given i.p. daily for two weeks at a concentration of 3.23 mg/kg. However, the antineoplastic properties of OU were unknown. We assessed the ability of OU to inhibit the proliferation of various human tumor cell lines (3 pancreatic, 1 colon, 1 neuroendocrine, and 1 lung) in an in vitro radiometric (Bactec) system. In the pancreatic lines (RWP-2, MiaPaCa-2, and PANC-1), the colon line (HT-29), the neuroendocrine line (COLO 320DM), and the lung cancer cell line (SK-MES-1), OU at a concentration of 10(3) microM, produced a dramatic decrease in percent cell survival. When compared with cytotoxic drugs of choice for these tumor cells (gemcitabine, 5-fluorouracil, and adriamycin, respectively) a significantly higher concentration of OU was required usually to achieve comparable results with two exceptions. These were the HT-29 and the COLO 320DM cell lines. These results indicate OU has significant (p < 0.05) cytotoxic activity against pancreatic, colon, neuroendocrine, and nonsmall cell lung cancer lines, when compared to untreated control cultures. Additional in vivo testing of this potential antineoplastic agent is warranted.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology*
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Fluorouracil / pharmacology
  • Humans
  • Oxazines / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antimetabolites, Antineoplastic
  • Oxazines
  • 3-oxauracil
  • Fluorouracil