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Welcoming Bruno Gonçalves to the group

Dr. Bruno Gonçalves was hired to work on the project entitled Multidrug Resistance Reversal in Cancer: Natural Compounds as P-glycoprotein and Breast Cancer Resistance Protein Modulators. This project is financed by the Portuguese Science Foundation (FCT) to discover and develop Read more ›

Terpenoids from Euphorbia pedroi as Multidrug-Resistance Reversers

The phytochemical study of Euphorbia pedroi led to the isolation of a new tetracyclic triterpenoid with an unusual spiro scaffold, spiropedroxodiol (1), along with seven known terpenoids (2–8). Aiming at obtaining compounds with improved multidrug-resistance (MDR) reversal activity, compound 8, Read more ›

Optimizing the flavanone core toward new selective nitrogen-containing modulators of ABC transporters

Aim: Naringenin (1), isolated in large amount from the aerial parts of Euphorbia pedroi, was chemically derivatized to yield 18 imine derivatives (2–19) and three alkylated derivatives through a Mannich-type reaction (20–22) that were tested as multidrug resistance (MDR) reversers Read more ›

About P-glycoprotein: a new drugable domain is emerging from structural data

P-glycoprotein (P-gp) has been considered an important molecular target in the reversal of multidrug resistance (MDR). As such, the development of P-gp modulators able to restore drug sensitivity in resistant cells is still considered one of the most promising strategies Read more ›

Optimizing the macrocyclic diterpenic core toward the reversal of multidrug resistance in cancer

Background: From a dataset obtained by chemical derivatization of a macrocyclic diterpenic scaffold, in silico approaches identified which structural features correlate with experimental modulation of P-gp activity. Results/methodology: Ninety-two percent of the strongest MDR modulators were positively identified within the Read more ›

Do Drugs Have Access to the P-Glycoprotein Drug-Binding Pocket through Gates?

The P-glycoprotein efflux mechanism is being studied since its identification as a leading protagonist in multidrug resistance. Recently, it was suggested that drugs enter the drug-binding pocket (DBP) through gates located between the transmembrane domains. For both a substrate and Read more ›

Do adsorbed drugs onto P-glycoprotein influence its efflux capability?

The membrane biophysical aspects by which multidrug resistance (MDR) relate to the ABC transporter function still remain largely unknown. Notwithstanding the central role that efflux pumps like P-glycoprotein have in MDR onset, experimental studies classified additionally the lipid micro-environment where Read more ›

P-glycoprotein and membrane roles in multidrug resistance

Multidrug-resistance (MDR) phenomena are a worldwide health concern. ATP-binding cassette efflux pumps as P-glycoprotein have been thoroughly studied in a frantic run to develop new efflux modulators capable to reverse MDR phenotypes. The study of efflux pumps has provided some Read more ›

Reversing cancer multidrug resistance: insights into the efflux by ABC transports from in silico studies

One of the greatest threats to cancer treatment is the development, by some tumors, of resistance to the pharmacological action of several structurally unrelated cytotoxic agents—multidrug resistance (MDR). As P-glycoprotein (P-gp) is one of the most studied ATP-dependent efflux pumps Read more ›

Molecular Docking Characterizes Substrate-Binding Sites and Efflux Modulation Mechanisms within P-Glycoprotein

P-Glycoprotein (Pgp) is one of the best characterized ABC transporters, often involved in the multidrug-resistance phenotype overexpressed by several cancer cell lines. Experimental studies contributed to important knowledge concerning substrate polyspecificity, efflux mechanism, and drug-binding sites. This information is, however, Read more ›