Benzoquinazoline inhibitors of thymidylate synthase: enzyme inhibitory activity and cytotoxicity of some sulfonamidobenzoylglutamate and related derivatives.

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Pendergast W, Dickerson SH, Johnson JV, Dev IK, Ferone R, Duch DS, Smith GK

Benzoquinazoline inhibitors of thymidylate synthase: enzyme inhibitory activity and cytotoxicity of some sulfonamidobenzoylglutamate and related derivatives.

J Med Chem. 1993 Oct 29;36(22):3464-71.

PubMed ID

8230138 [ View in PubMed

]

Abstract

Several folate-like thymidylate synthase inhibitors are described in which the pteridine nucleus of the folic acid molecule is replaced by a benzoquinazoline moiety, which in turn is attached to the benzoylglutamate side chain by a sulfonamide link. The most potent compounds had Ki values as low as 2.5 nM against the human enzyme, were good substrates for the cellular reduced folate transport system and for folylpolyglutamate synthetase, and had IC50 values for growth inhibition of tumor cell lines as low as 70 nM.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
10-Propargyl-5,8-Dideazafolic Acid	Thymidylate synthase	IC 50 (nM)	20	N/A	N/A	Details