سنتز پيش دارويي از دوكسوروبيسين بعنوان تركيبي بالقوه موثر در درمان سرطان پستان

Synthesis of a novel Doxorubicin-prodrug as a potential anti-breast Cancer agent

Breast cancer is the most important kind of cancer in pre and postmenopausal women. In the treatment of cancers, spacially metastatic breast cancer, doxorubicin has the broadest spectrum among of any drugs presently available, but it produces a dose dependent cardiomyopathy and other side effects which limit its clinical usefulness. To overcome this undesired side effect, one solution was to synthesis doxorubicin based prodrugs which can specifically enter into tumor cells, with less distribution in normal tissues. For this purpose estrogen receptors, present in higher amount in cancer cells than normal one, was considered as a target and therefore doxorubicin was linked to estrone as a compound with high affinity to estrogen receptors. In this study, first the 17-keto group of estrone was linked to amine groups on spacer groups such as 4-amino-l-butanol or 5-amino-l-pentanol via setoffʹs base reaction to prepare an imine functional group that readily reduce to an amine compound. Then resulted amine was reacted with succinic anhydride to yield an acidic derivative of estrone. Isobutylchloro formate, afterwards, was used to catalys the final reaction that was an amide bond formation between carboxylic derivative of estrone and amine group located on the danosamine moiety of doxorubicin to yield the final proposed prodrug in 43%. Analytical spectrometric methods such as IR, MS and NMR confirmed the successful synthesis of doxorubicin-estrone prodrug which is potentially active against estrogen receptor positive breast cancers.