Intestinal P-glycoprotein inhibitors, benzoxanthone analogues.Ĭhae, Song Wha Lee, Jaeok Park, Jung Hyun Kwon, Youngjoo Na, Younghwa Lee, Hwa Jeong After a two-step (internal/external) validation, the best-performing classification models were used in a consensus predicting task for the identification of compounds named as 'true' P-gp inhibitors, i.e., molecules able to inhibit P-gp without being effluxed by P-gp itself and simultaneously unable to activate the ATPase function. Rational splitting was accomplished using a sphere-exclusion type algorithm. For each experiment, the dataset was split into a training and a test set comprising 39 and 20 molecules, respectively. This study aims to develop classification models from a unique dataset of 59 compounds for which there were homogeneous experimental data on P-gp inhibition, ATPase activation and monolayer efflux. P-gp inhibition may be considered as a valid approach to improve drug bioavailability as well as to overcome drug resistance to many kinds of tumours characterized by the over-expression of this protein. The development of new and more effective therapeutics targeting P-gp thus represents an intriguing challenge in drug discovery. P-gp plays a key role in multidrug resistance and in the progression of many neurodegenerative diseases. P-glycoprotein ( P-gp) is an efflux pump involved in the protection of tissues of several organs by influencing xenobiotic disposition. Rapposelli, Simona Coi, Alessio Imbriani, Marcello Bianucci, Anna Maria

PMID:24451193ĭevelopment of classification models for identifying 'true' P-glycoprotein ( P-gp) inhibitors through inhibition, ATPase activation and monolayer efflux assays.

Natural compounds that modulate P-gp offer great possibilities for semi-synthetic modification to create new drugs and are valuable research tools to understand the function of complex ABC transporters. This review article aims to summarize the research findings on the marine natural products with P-glycoprotein inhibitor properties. P-gp is a major cause of drug resistance in cancer, parasitic diseases, epilepsy and other disorders. P-glycoprotein ( P-gp) is a protein belonging to the ATP-binding cassette (ABC) transporters superfamily that has clinical relevance due to its role in drug metabolism and multi-drug resistance (MDR) in several human pathogens and diseases.

Marine Natural Products with P-Glycoprotein Inhibitor Properties

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