Related Experiment Video

Updated: May 24, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

Activity of fourteen new hydantoin compounds on the human ABCB1 efflux pump

Ana Martins1, Anna Dymek, Jadwiga Handzlik

  • 1Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary.

In Vivo (Athens, Greece)
|February 22, 2012
PubMed
Abstract

Insights

New hydantoin compounds show promise in overcoming multidrug resistance (MDR) in cancer by modulating ABCB1 transporter activity. This research identifies key structural features for developing more effective cancer therapies.

Area of Science:

  • Medicinal Chemistry
  • Cancer Biology
  • Pharmacology

Background:

  • Multidrug resistance (MDR) is a significant challenge in cancer treatment, often linked to ABCB1 transporter overexpression.
  • ABCB1 transporter activity is a key factor in cancer therapy failure.
  • Hydantoin compounds have demonstrated potential in modulating ABCB1 pump activity.

Purpose of the Study:

  • To synthesize and evaluate novel hydantoin derivatives for their ability to overcome ABCB1-mediated MDR.
  • To identify structure-activity relationships among the synthesized hydantoins.

Main Methods:

  • Synthesis of fourteen hydantoin derivatives.
  • Assay of hydantoin derivatives' capacity to increase ethidium bromide (EB) accumulation in ABCB1-overexpressing mouse lymphoma cancer cells.

Main Results:

  • Four hydantoin derivatives significantly increased EB accumulation, indicating potent ABCB1 modulation.
  • Seven additional hydantoins showed milder effects, while three were inactive.
  • Structure-activity relationship analysis identified key molecular substituents responsible for enhanced activity.

Conclusions:

  • The study identified active hydantoin compounds with potential to reverse ABCB1-mediated MDR.
  • Structure-activity relationship insights pave the way for designing more potent anticancer agents.
  • Further research and synthesis of novel hydantoins are warranted to develop effective MDR-targeting therapies.

More Related Videos

Characterizing Multidrug Efflux Systems in Acinetobacter baumannii Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System05:06

Characterizing Multidrug Efflux Systems in Acinetobacter baumannii Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System

Published on: January 5, 2024

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport08:42

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport

Published on: November 27, 2016

Related Concept Videos

ABC Transporters: Exporter01:31

ABC Transporters: Exporter

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
ABC Transporters: Importer01:27

ABC Transporters: Importer

ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Hepatic Drug Clearance: Role of Transporters01:14

Hepatic Drug Clearance: Role of Transporters

In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
Active Transport01:14

Active Transport

Active transport is a critical biological process that allows cells to move solutes against an electrochemical gradient. This process requires direct energy input and is characterized by its selectivity, saturability, and susceptibility to competitive inhibition.
Primary active transporters, like Na+, K+ and -ATPase, directly utilize ATP to move ions across the membrane. These transporters play significant roles in various physiological processes. For instance, Na+, K+ and -ATPase maintain...