In vitro antineoplastic activity of C7-substituted mitomycin C analogues MC-77 and MC-62 against human breast-cancer cell lines

Alem Ghiorghis, Abdolhossen Talebian, Robert Clarke

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Mitomycin C (MIT-C) is one of the most potent antineoplastic agents used for the treatment of breast cancer and a wide variety of malignant tumors. However, administration of MIT-C is frequently accompanied by the delayed onset of severe myelosuppression. We have synthesized a new series of MIT-C analogues that are predicted on a structure/function basis to retain cytotoxicity but exhibit decreased toxicity. These new compounds feature a sugar substitution at the N7 position. Using a series of human breast-cancer cell lines growing in vitro, we determined the structure/activity relationship of two independent N7-substituted spacers displaying the same glucopyranose moiety. N-{[(2-acetamide-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)amino]carbonyl} propylmitomycin C (MC-62) contains the sugar moiety linked to MIT-C through a butanoic acid spacer. MC-62 exhibits significantly less biological potency as compared with the parent drug. In contrast, N-[4-(tetra-O-acetylglucopyranosyl)oxy]phenylmitomycin C (MC-77) contains the glucopyranose moiety linked to MIT-C through a phenolic spacer. This analogue generally exhibits greater antitumor activity in vitro as compared with either MC-62 or MIT-C. Thus, N7-substituted analogues containing sugar moieties exhibit altered biological activity, the degree of which is related to the properties/structure of the spacer.

Original languageEnglish (US)
Pages (from-to)290-296
Number of pages7
JournalCancer chemotherapy and pharmacology
Volume29
Issue number4
DOIs
StatePublished - Jul 1992
Externally publishedYes

Fingerprint Dive into the research topics of 'In vitro antineoplastic activity of C7-substituted mitomycin C analogues MC-77 and MC-62 against human breast-cancer cell lines'. Together they form a unique fingerprint.

  • Cite this