Prolidase as a prodrug converting enzyme. II. Synthesis of proline analogue of anthraquinone-2-carboxylic acid and its susceptibility to the action of prolidase.
The feasibility to targeting prolidase as an antineoplastic prodrug--converting enzyme has been examined. The synthesis of proline analogue of anthraquinone-2-carboxylic acid (potential antineoplastic agent) conjugated through imido-bond (potential target for prolidase action) has been performed. The product was found to be insoluble in aqueous solution while in the presence of 1% DMSO complete solubility of the compound was achieved. Evidence was provided that 1% DMSO does not affect prolidase activity, thus allowing for substrate susceptibility measurement in a such conditions. It has been presented that product of synthesis, N-(anthraquinone-2-carbonyl)-L-proline evokes susceptibility to the action of purified prolidase, comparable to the susceptibility of glycyl-L-proline (standard substrate for prolidase). Although insolubility of the proline analogue of anthraquinone-2-carboxylic acid in aqueous solutions limit its potential therapeutic value, the presented data suggest that prolidase may have a broader substrate specificity than thought previously. It suggests that targeting of prolidase as a prodrug-converting enzyme may serve as a potential strategy in therapy of neoplastic diseases.
Bielawska
A
A
Department of Medicinal Chemistry and Drug Technology, Medical Academy of Białystok.
Bielawski
K
K
Pałka
J
J
D000880:Anthraquinones / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D004150:Dipeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D011355:Prodrugs / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D012995:Solubility