Related Experiment Video

Updated: May 22, 2026

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

Colon adenocarcinoma multidrug resistance reverted by Euphorbia diterpenes: structure-activity relationships and

Mariana Reis1, Ricardo J Ferreira, Julianna Serly

  • 1Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculdade de Farmacia, Universidade de Lisboa, Av. Prof. Gama Pinto 1649-003, Lisboa, Portugal. mjuferreira@ff.ul.pt

Anti-Cancer Agents in Medicinal Chemistry
|May 16, 2012
PubMed

Insights

Natural compounds from Euphorbia species show promise in reversing multidrug resistance (MDR) in cancer by inhibiting P-glycoprotein (P-gp) efflux. These findings could lead to more effective chemotherapy treatments.

Area of Science:

  • Medicinal Chemistry
  • Pharmacology
  • Cancer Biology

Background:

  • Multidrug resistance (MDR) significantly limits chemotherapy efficacy.
  • P-glycoprotein (P-gp) mediated drug efflux is a primary mechanism of MDR.

Purpose of the Study:

  • To investigate the P-gp inhibitory and MDR reversal activities of macrocyclic diterpenes and polycyclic derivatives from Euphorbia species.
  • To establish structure-activity relationships (SAR) and develop a pharmacophore model for P-gp inhibitors.

Main Methods:

  • Screening of sixteen Euphorbia derivatives using MDR human colon adenocarcinoma cells (COLO 320 MDR).
  • Statistical analysis (K-means clustering, Principal Component Analysis) to correlate physicochemical properties with activity.
  • In vitro testing of lead compounds in combination with doxorubicin.
  • Pharmacophore modeling and molecular docking studies.

Main Results:

  • Most tested compounds exhibited MDR reversal potential.
  • A strong correlation between log P and MDR reversal activity was observed for compounds 1-5.
  • Compounds 1-4 and 11-12 potentiated doxorubicin activity, reducing its IC50.
  • A new five-point pharmacophore model was developed, highlighting the importance of an aromatic moiety for enhanced P-gp inhibitory activity.

Conclusions:

  • Macrocyclic diterpenes and polycyclic derivatives from Euphorbia species are effective MDR reversal agents.
  • The study identified key structural features, including an aromatic moiety, crucial for P-gp inhibition.
  • These findings offer a basis for designing novel P-gp inhibitors to overcome chemotherapy resistance.

More Related Videos

A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products07:59

A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products

Published on: October 4, 2019

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling09:33

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling

Published on: March 20, 2018

Related Concept Videos

Structure-Activity Relationships and Drug Design01:28

Structure-Activity Relationships and Drug Design

Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence its...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Adrenergic Agonists: Chemistry and Structure-Activity Relationship01:16

Adrenergic Agonists: Chemistry and Structure-Activity Relationship

Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...