Allelix Biopharmaceuticals Inc.

Allelix, Inc.

Anne E Goodbody

John Vukovic

Yan Xu

Masanaru Misawa

Endo Tsuyoshi

Colin D Watson

Herein described is an ovarian cancer activating factor that has been isolated from ovarian cancer ascites fluid. The factor may be utilized in its isolated form in a screening program aimed at identifying inhibitors of factor-mediated ovarian cancer activation, or as a growth supplement useful for culturing ovarian and other cancer cell lines.

Ovarian cancer ascites factor, in isolated form

3',4'-anhydrovinblastine, a precursor of the anti-tumor alkaloids vincristine and vinblastine, is prepared by the enzymatic coupling of catharanthine and vindoline using an iron-containing compound such as peroxidase optionally in the presence of a peroxide. Substantially enhanced yields are obtained.

Enzymatic preparation of 3',4'-anhydrovinblastine

Alkaloids present in Catharanthus roseus tissue are selectively concentrated by aqueous extraction of ground tissue followed by extraction with organic solvent e.g. ethyl acetate. The resultant concentrate is rich in catharanthine, vindoline and 3',4'-anhydrovinblastine (AVLB). Yield of AVLB is enhanced by addition to the aqueous extraction medium of acid, salt, or hydrogen peroxide and can be further enhanced through the addition of sodium borohydride.

Extraction of alkaloids of Catharanthus roseus tissue

Alkaloid dimers are formed by coupling vindoline and catharanthine in the presence of ferric ion. The predominant products are 3',4'-anhydrovinblastine and vinblastine when reaction conditions are selected appropriately.

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Toronto, Canada

Anne E Goodbody