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Convergent synthesis of a steroidal antiestrogen-mitomycin C hybrid using "click" chemistry.

ABSTRACT: A convergent synthesis of a novel estrogen receptor-targeted drug hybrid was developed based on structures of the potent anti-proliferative mitomycin C and the steroidal anti-estrogen RU 39411. The steroidal antiestrogen was prepared with an azido-triethylene glycoloxy linker while the mitomycin C derivative (porfirimycin) incorporated a complementary 7-N-terminal alkyne. The two components were ligated using the Huisgen [3 + 2] cycloaddition ("click") reaction. Preliminary biological assays demonstrated that the final hybrid compound retained both potent anti-estrogenic and anti-proliferative activities.

SUBMITTER: Hanson RN

PROVIDER: S-EPMC3519291 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Convergent synthesis of a steroidal antiestrogen-mitomycin C hybrid using "click" chemistry.

Hanson Robert N RN Hua Edward E Labaree David D Hochberg Richard B RB Proffitt Kyle K Essigmann John M JM Croy Robert G RG

Organic & biomolecular chemistry 20120925 42

A convergent synthesis of a novel estrogen receptor-targeted drug hybrid was developed based on structures of the potent anti-proliferative mitomycin C and the steroidal anti-estrogen RU 39411. The steroidal antiestrogen was prepared with an azido-triethylene glycoloxy linker while the mitomycin C derivative (porfirimycin) incorporated a complementary 7-N-terminal alkyne. The two components were ligated using the Huisgen [3 + 2] cycloaddition ("click") reaction. Preliminary biological assays dem ...[more]

PMID: 23007562

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