Disulfiram inhibits activating transcription factor/cyclic AMP-responsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease.

The thiocarbamate alcoholism drug disulfiram blocks the P-glycoprotein extrusion pump, inhibits the transcription factor nuclear factor-kappaB, sensitizes tumors to chemotherapy, reduces angiogenesis, and inhibits tumor growth in mice. Thiocarbamates react with critical thiols and also complex metal ions. Using melanoma as the paradigm, we tested whether disulfiram might inhibit growth by forming mixed disulfides with critical thiols in a mechanism facilitated by metal ions.

Thermally-prepared polymorphic forms of cilostazol.

Prior to this study, cilostazol, an antithrombotic drug, was thought to exist as a single crystalline phase with a melting point of approximately 159 degrees C (Form A). On cooling, melts often form a glass that, when heated, may crystallize as additional crystalline polymorphic forms. Cilostazol, when reheated, subsequently forms polymorphs that melt at approximately 136 degrees C (Form B) and 146 degrees C (Form C).

Polymorphic forms of cilostazol.

Two unique conformational polymorphic forms of the compound 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydroquinolin-2(1H)-one (cilostazol), C(20)H(27)N(5)O(2), have been discovered and characterized using single-crystal X-ray structural analysis. A third polymorph also exists, but acceptable crystals could not be obtained. Features of both reported polymorphic structures include a chair conformation of the cyclohexyl ring and puckering in the quinolinone ring.