The present invention is directed to compounds that are specifically structured to provide enzyme inhibition. In specific embodiments, the enzyme inhibiting compounds exhibit antifolate activity. Particularly, the inventive compounds are formed of an antifolate residue that is active in inhibiting one or more of TS, DHFR, GARFT, and AICAR Tfase. The enzyme inhibiting compounds are useful in a variety of methods of treatment, including treating abnormal cell proliferation and treating inflammation.
