- Synthesis and biological evaluation of dual action cyclo-RGD/SMAC mimetic conjugates targeting αvβ3/α vβ5 integrins and IAP proteins
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The rational design, synthesis and in vitro biological evaluation of dual action conjugates 11-13, containing a tumour targeting, integrin αvβ3/αvβ5 ligand portion and a pro-apoptotic SMAC mimetic portion (cyclo-RGD/SMAC mimetic conjugates) are reported. The binding strength of the two separate units is generally maintained by these dual action conjugates. In particular, the connection between the separate units (anchor points on each unit; nature, length and stability of the linker) influences the activity of each portion against its molecular targets (integrins αvβ3/ αvβ5 for cyclo-RGD, IAP proteins for SMAC mimetics). Each conjugate portion tolerates different substitutions while preserving the binding affinity for each target.
- Mingozzi,Manzoni,Arosio,Dal Corso,Manzotti,Innamorati,Pignataro,Lecis,Delia,Seneci,Gennari
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supporting information
p. 3288 - 3302
(2014/05/06)
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- Progesterone-adenine hybrids as bivalent inhibitors of P-glycoprotein- mediated multidrug efflux: Design, synthesis, characterization and biological evaluation
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Bivalent ligands were designed on the basis of the described close proximity of the ATP-site and the putative steroid-binding site of P-glycoprotein (ABCB1). The syntheses of 19 progesterone-adenine hybrids are described. Their abilities to inhibit P-glycoprotein-mediated daunorubicin efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein were evaluated versus progesterone. The hybrid with a hexamethylene linker chain showed the best inhibitory potency. The efficiency of these progesterone-adenine hybrids depends on two main factors: (i) the nature of the linker and (ii) its attachment point on the steroid skeleton.
- Zeinyeh, Wael,Mahiout, Zahia,Radix, Sylvie,Lomberget, Thierry,Dumoulin, Axel,Barret, Roland,Grenot, Catherine,Rocheblave, Luc,Walchshofer, Nadia,Matera, Eva-Laure,Dumontet, Charles
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p. 1177 - 1191,15
(2020/08/20)
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- Design, synthesis and evaluation of progesterone-adenine hybrids as bivalent inhibitors of P-glycoprotein-mediated multidrug efflux
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Steroidal bivalent ligands were designed on the basis of the described closer proximity of the ATP-site and the putative steroid-binding site of P-glycoprotein (ABCB1). The syntheses of seven progesterone-adenine hybrids were described. Their abilities to inhibit P-glycoprotein-mediated daunorubicin efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein were evaluated versus progesterone.
- Zeinyeh, Wa?l,Alameh, Ghina,Radix, Sylvie,Grenot, Catherine,Dumontet, Charles,Walchshofer, Nadia
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scheme or table
p. 3165 - 3168
(2010/09/05)
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