UK-1 analogues: methods of preparation and use

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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C514S613000, C548S224000, C564S161000

Reexamination Certificate

active

10720991

ABSTRACT:
The present invention includes a number of structural analogues of UK-1. A comparision of the anticancer activity of the UK-1 analogues with their ability to inhibit the growth of methicillin-sensitive and methicillin-resistantStaphylococcus aureusdemonstrates that a structurally simplified analogue of UK-1 retains the natural product's selective activity against cancer cells. Structurally conservative changes to UK-1 that diminish Mg2+-binding ability may result in a dramatic decrease in cancer cell cytotoxicity. The results may establish a minimum structural pharmacophore as well as a functional role for Mg2+-binding in the selective cytotoxicity of UK-1.

REFERENCES:
Dunwell, David et al, “Synthesis & Antiinflammatory Activity of Some 2-aryl-6-benzoxazoleacetic Acid Derivatives,” J. Med. Chem, 1977, 20 (6), pp. 797-801.
DeLuca et al., “The Total Synthesis of UK-1”, Tetrahedron Letters, 38:2(1997) 199-202.
Ahmed et al., “A new rapid and simple non-radioactive assay to monitor and determine the proliferation of lymphocytes: an alternative to [3H] thymidine incorporation assay”, Journal of Immunological Methods, 170(1994) 211-224.
Likussar et al., “Theory of Continuous Variations Plots and a New Method of Spectophotometric Determination of Extraction and Formation Constants”, Analytical Chemistry, 43:10(1971) 1265-1272.

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