Targeting lysosomes by design: novel <i>N</i>-acridine thiosemicarbazones that enable direct detection of intracellular drug localization and overcome P-glycoprotein (Pgp)-mediated resistance
Büşra Kaya, Henry R. Smith, Yanbing Chen, Mahan Gholam Azad, Tiffany M. Russell, Věra Richardson, Paul V. Bernhardt, Mahendiran Dharmasivam, Des R. Richardson
Abstract
Inclusion of the acridine moiety into the thiosemicarbazone framework of NATs facilitates their function as lysosomotropic substrates for P-glycoprotein (Pgp). This promotes lysosomal targeting and effectively overcomes Pgp-mediated drug resistance.
Topics & Concepts
IntracellularAcridineP-glycoproteinChemistryCell biologyGlycoproteinAutophagyDrug resistanceBiochemistryBiologyMultiple drug resistanceMicrobiologyAntibioticsApoptosisOrganic chemistryDrug Transport and Resistance MechanismsMetal complexes synthesis and propertiesHIV/AIDS drug development and treatment