Abstract

Starting from the previously developed P-gp ligands 1a and 1b (EC50 ¼ 0.25 mM and 0.65 mM, respectively), new arylmethyloxyphenyl derivatives have been synthesized as P-gp modulators in order to investigate: (i) the effect of small electron-donor groups (OMe) (5e11), (ii) the effect of the replacement of methoxy groups with an electron-withdrawal substituent (Cl) on C-ring (13) (iii) the effect induced by the replacement of C-ring with heteroaromatic cycles such as thiophene and pyrimidine (13, 15, 16), (iv) the effect induced by molecular constriction on C ring (14, 17, 18) on P-gp modulating activity. The results demonstrated that P-gp inhibition potency is strongly correlated to the number of methoxy groups in the A-ring whereas the methoxylation of C-ring seems to poorly affect P-gp activity. The best result was found for compound 10 that displays a nanomolar affinity (EC50 ¼ 7.1 nM) towards P-gp pump and, in the meantime lacks of activity against MRP1 pump.

Autore Pugliese

• Perrone Maria Grazia , Contino Marialessandra , Colabufo Nicola Antonio

Tutti gli autori

• PERRONE M.G.;CONTINO M.;COLABUFO N.A.;PERRONE R.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2014

ISSN

0223-5234

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

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Numero di citazioni Scopus

5

Ultimo Aggiornamento Citazioni

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Settori ERC

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Codici ASJC

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