Abstract
Thiol reagents were shown to act as potent inhibitors of L5178-Y murine leukemia cell proliferation. A series of aryl maleimides (AMI) was synthesized and evaluated theoretically for global and local reactivity, showing their selectivity for thiol groups, due to a reaction of the vinyl moiety (a soft acid) with thiols (a soft base). Two AMI that are benzoic acid derivatives (1f and 1h) were tested with an in vitro and ex vivo model to evaluate their reactivity with thiols and their activity in L5178-Y cells. The in vitro reactions clearly showed a selective Michael type 1,4-addition reaction between thiols (glutathione and N-acetylcysteine, which are nucleophiles) and the AMI (1f and 1h, which are electrophiles). In cell cultures, the compounds induced a decreasing cellular viability and an apoptotic effect of up to 59.8% at 48 h. The ex vivo experimental model showed an important reduction of thiol levels in cells treated with 1h. Decreased cellular viability and increased apoptosis were confirmed by flow cytometry, DNA fragmentation and microscopy analysis (cytological studies). The increase in apoptosis on L5178-Y cells probably occurred, at least in part, by a decrease in glutathione levels and an increase in free radicals concentration. The decreased glutathione levels seem to make cancer cells more susceptible to death by apoptosis, and should certainly make them more vulnerable to a less aggressive treatment.
Keywords: Anticancer, apoptosis, global reactivity, glutathione, local reactivity, aryl maleimides.
Anti-Cancer Agents in Medicinal Chemistry
Title:Aryl Maleimides as Apoptosis Inducers on L5178-Y Murine Leukemia Cells (in silico, in vitro and ex vivo Study)
Volume: 16 Issue: 12
Author(s): Erik Andrade-Jorge, Marycarmen Godínez-Victoria, Luvia Enid Sánchez-Torres, Luis Humberto Fabila-Castillo and José G. Trujillo-Ferrara
Affiliation:
Keywords: Anticancer, apoptosis, global reactivity, glutathione, local reactivity, aryl maleimides.
Abstract: Thiol reagents were shown to act as potent inhibitors of L5178-Y murine leukemia cell proliferation. A series of aryl maleimides (AMI) was synthesized and evaluated theoretically for global and local reactivity, showing their selectivity for thiol groups, due to a reaction of the vinyl moiety (a soft acid) with thiols (a soft base). Two AMI that are benzoic acid derivatives (1f and 1h) were tested with an in vitro and ex vivo model to evaluate their reactivity with thiols and their activity in L5178-Y cells. The in vitro reactions clearly showed a selective Michael type 1,4-addition reaction between thiols (glutathione and N-acetylcysteine, which are nucleophiles) and the AMI (1f and 1h, which are electrophiles). In cell cultures, the compounds induced a decreasing cellular viability and an apoptotic effect of up to 59.8% at 48 h. The ex vivo experimental model showed an important reduction of thiol levels in cells treated with 1h. Decreased cellular viability and increased apoptosis were confirmed by flow cytometry, DNA fragmentation and microscopy analysis (cytological studies). The increase in apoptosis on L5178-Y cells probably occurred, at least in part, by a decrease in glutathione levels and an increase in free radicals concentration. The decreased glutathione levels seem to make cancer cells more susceptible to death by apoptosis, and should certainly make them more vulnerable to a less aggressive treatment.
Export Options
About this article
Cite this article as:
Andrade-Jorge Erik, Godínez-Victoria Marycarmen, Sánchez-Torres Enid Luvia, Fabila-Castillo Humberto Luis and Trujillo-Ferrara G. José, Aryl Maleimides as Apoptosis Inducers on L5178-Y Murine Leukemia Cells (in silico, in vitro and ex vivo Study), Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (12) . https://dx.doi.org/10.2174/1871520615666160504094417
DOI https://dx.doi.org/10.2174/1871520615666160504094417 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Robust Pulmonary Nodule Segmentation in CT Image for Juxta-pleural and Juxta-vascular Case
Current Bioinformatics Concerns and Considerations about the Quality Control of Natural Products Using Chromatographic Methods
Current Chromatography An Overview on Natural Polysaccharides with Antioxidant Properties
Current Medicinal Chemistry Perfluoroalkylsulfonyloxyisoflavones: Synthesis and Anti-Proliferation of HL-60
Letters in Organic Chemistry Nano Hydroxyapatite (nano-HAp): A Potential Bioceramic for Biomedical Applications
Current Nanomaterials Improving Functional Modules Discovery by Enriching Interaction Networks with Gene Profiles
Current Bioinformatics Carbon Quantum Dots: Surface Passivation and Functionalization
Current Organic Chemistry Molecular Targets of Tannic Acid in Alzheimer's Disease
Current Alzheimer Research Metabolite Interference in Pharmacokinetic Studies
Drug Metabolism Letters Glycan-Binding Profile and Cell Adhesion Activity of American Bullfrog (Rana catesbeiana) Oocyte Galectin-1
Protein & Peptide Letters Benzothiazole Derivatives: Novel Inhibitors of Methylglyoxal Mediated Glycation of Proteins In Vitro
Medicinal Chemistry Magnetic Materials for the Selective Analysis of Peptide and Protein Biomarkers
Current Medicinal Chemistry Molecular Determinants of Chronic Liver Disease as Studied by NMR-Metabolomics
Current Topics in Medicinal Chemistry Applications and Toxicity of Silver Nanoparticles: A Recent Review
Current Topics in Medicinal Chemistry The Renin-Angiotensin System: Emerging Concepts
Current Hypertension Reviews 1,2,4-Oxadiazoles Identified by Virtual Screening and their Non-Covalent Inhibition of the Human 20S Proteasome
Current Medicinal Chemistry Triterpenoids for Cancer Prevention and Treatment: Current Status and Future Prospects
Current Pharmaceutical Biotechnology Stationary Wavelet Transform and AdaBoost with SVM Based Pathological Brain Detection in MRI Scanning
CNS & Neurological Disorders - Drug Targets Microfluidic Devices for Cell, Tissue and Embryo Culture
Recent Patents on Regenerative Medicine Supramolecular Polymer Complexes Based on Specific Molecular Recognition: DNA and its Synthetic Mimics
Current Organic Chemistry