| Abstract: |
A novel 5-o-carboranyl-containing nucleoside, 5-o-carboranyl-1-(2-deoxy-2-fluoro-β-d-arabinofuranosyl) uracil (6, CFAU), was synthesized as a potential intracellular neutron capture agent. This compound was prepared in five steps starting from 5-iodo-1-(2-deoxy-2-fluoro-β-d-arabinofuranosyl) uracil (1). The desired carboranyl derivative was obtained by addition of decaborane [as the bis(propionitrile) adduct] to the protected acetylenic nucleoside precursor followed by debenzoylation. The synthesis of CFAU was also performed by glycosylation of the suitably protected 5-o-carboranyluracil with the appropriate 2-fluoroarabinosyl derivative. This compound was evaluated for its cytotoxicity in human lymphocytes, monkey cells, and rat and human gliomas cells, as well as for antiviral activity against human immunodeficiency virus and herpes simplex virus type 1. Its biological activity was compared to 5-o-carboranyl-1-(2-deoxyribofuranosyl)uracil in these cell culture systems, human bone marrow cells, and mice. The results obtained to date suggest that CFAU has suitable characteristics as a sensitizer for boron neutron capture therapy. © 1994, American Chemical Society. All rights reserved. |
| Keywords: |
controlled study; unclassified drug; human cell; dose response; nonhuman; human immunodeficiency virus infection; glioma; animal cell; mouse; animal; mice; cell survival; melanoma; bone marrow; animal experiment; cytotoxicity; drug structure; tumor cells, cultured; drug synthesis; glycosylation; uracil arabinoside; arabinofuranosyluracil; herpesvirus 1, human; rats; radiation-sensitizing agents; lymphocytes; herpes simplex virus 1; cancer cell destruction; antiviral activity; colony forming unit gm; vero cell; hiv-1; zidovudine; antiviral agents; boron compounds; burst forming unit e; neutron capture therapy; human; female; article; boron neutron capture therapy; fluorouracil derivative; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; support, u.s. gov't, non-p.h.s.; 5 carboranyl 2' deoxyuridine; 5 o carboranyl 1 (2 deoxy 2 fluoro beta d arabinofuranosyl)uracil; carborane derivative
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