Abstract
Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target.
Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38).
Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines (IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and 16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 = 22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3 and MCF-7 respectively with no cytotoxicity against WI-38.
Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize their molecular mechanism as cytotoxic agents.
Keywords: 2-Thioxoimidazolidinone, mannich reaction, prostate cancer, breast cancer, topoisomerase I, synthesis.
Anti-Cancer Agents in Medicinal Chemistry
Title:Design, Synthesis and Cytotoxicity Evaluation of New 3, 5-Disubstituted-2-Thioxoimidazolidinones
Volume: 18 Issue: 4
Author(s): Khaled R.A. Abdellatif*, Mostafa M. Elbadawi, Mohammed T. Elsaady, Amer A. Abd El-Hafeez, Takashi Fujimura, Seiji Kawamoto and Ahmed I. Khodair
Affiliation:
- Department of Pharmaceutical Organic Chemistry, Beni-Suef University, Beni-Suef 62514,Egypt
Keywords: 2-Thioxoimidazolidinone, mannich reaction, prostate cancer, breast cancer, topoisomerase I, synthesis.
Abstract: Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target.
Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38).
Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines (IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and 16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 = 22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3 and MCF-7 respectively with no cytotoxicity against WI-38.
Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize their molecular mechanism as cytotoxic agents.
Export Options
About this article
Cite this article as:
Abdellatif R.A. Khaled *, Elbadawi M. Mostafa , Elsaady T. Mohammed , Abd El-Hafeez A. Amer , Fujimura Takashi , Kawamoto Seiji and Khodair I. Ahmed, Design, Synthesis and Cytotoxicity Evaluation of New 3, 5-Disubstituted-2-Thioxoimidazolidinones, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (4) . https://dx.doi.org/10.2174/1871520618666171129213838
DOI https://dx.doi.org/10.2174/1871520618666171129213838 |
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
-
The Antidepressant-like Effects of Estrogen-mediated Ghrelin
Current Neuropharmacology Effects of Lipid-Lowering Drugs on Adiponectin
Current Vascular Pharmacology Insulin-like Growth Factor-1 Receptor (IGF-1R) Kinase Inhibitors in Cancer Therapy: Advances and Perspectives
Current Pharmaceutical Design Cytochrome P450 2W1 (CYP2W1) in Colorectal Cancers
Current Cancer Drug Targets Targeting the L-Arginine-Nitric Oxide Pathway for Cancer Treatment
Current Pharmaceutical Design Overview of SLC22A and SLCO Families of Drug Uptake Transporters in the Context of Cancer Treatments
Current Drug Metabolism From Natural Products to Designer Drugs: Development and Molecular Mechanisms Action of Novel Anti-Microtubule Breast Cancer Therapeutics
Current Topics in Medicinal Chemistry Novobiocin Analogs as Potential Anticancer Agents
Mini-Reviews in Medicinal Chemistry Carbon Nanotubes: Classification, Method of Preparation and Pharmaceutical Application
Current Drug Delivery Predictive Markers for Haematological Toxicity of Pemetrexed
Current Drug Targets A Review of Denoising Medical Images Using Machine Learning Approaches
Current Medical Imaging Antineoplastic Potential of Medicinal Plants
Recent Patents on Biotechnology Emerging Biologics in the Treatment of Inflammatory Bowel Disease: What is Around the Corner?
Current Drug Targets Raman, Infrared and NMR Spectroscopy: Advances in Structural, Conformational and Environmental Analysis
Combinatorial Chemistry & High Throughput Screening Radioiodinated Ginger Compounds (6-gingerol and 6-shogaol) and Incorporation Assays on Breast Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Dendrimer-Based Nanosized MRI Contrast Agents
Current Pharmaceutical Biotechnology Cytotoxicity, Docking Study of New Fluorinated Fused Pyrimidine Scaffold: Thermal and Microwave Irradiation Synthesis
Medicinal Chemistry β-Glucans: Old Molecules with Newly Discovered Immunological Activities
Drug Design Reviews - Online (Discontinued) Meet Our Section Editor:
Current Medicinal Chemistry Biological Activities of Eco-Friendly Synthesized Hantzsch Adducts
Medicinal Chemistry