- CARBONIC ANHYDRASE INHIBITORS WITH ANTIMETASTATIC ACTIVITY
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Compositions for the treatment of cancer comprising coumarin and thiocoumarin derivatives of Formulas I- XII are disclosed. Said derivatives preferentially inhibit carbonic anhydrase IX and XII (which are associated with hypoxic and metastatic tumours) over inhibiting carbonic anhydrase I and II activity. The compositions therefore are suited for treatment of hypoxic or metastatic cancers due to this selective mechanism of action.
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Page/Page column 22-29
(2012/06/15)
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- Glycosyl coumarin carbonic anhydrase IX and XII inhibitors strongly attenuate the growth of primary breast tumors
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A series of 7-substituted coumarins incorporating various glycosyl moieties were synthesized and investigated for the inhibition of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). These coumarins were very weak or ineffective as inhibitors of the housekeeping, offtarget isoforms CA I and II, but some of them inhibited tumor-associated CA IX and XII in the low nanomolar range. They also significantly inhibited the growth of primary tumors by the highly aggressive 4T1 syngeneic mouse mammary tumor cells at 30 mg/kg, constituting interesting candidates for the development of conceptually novel anticancer drugs. Because CA IX is overexpressed in hypoxic tumors and exhibits very limited expression in normal tissues, such compounds may be useful for treating cancers not responsive to classic chemo- and radiotherapy.
- Touisni, Nadia,Maresca, Alfonso,McDonald, Paul C.,Lou, Yuanmei,Scozzafava, Andrea,Dedhar, Shoukat,Winum, Jean-Yves,Supuran, Claudiu T.
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p. 8271 - 8277
(2012/02/06)
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