Abstract
Background: Although anticancer chemotherapeutics are available in markets, side effects related to the drugs in clinical use lead to researchers to investigate new drug candidates which are more safe, potent and selective than others. Chalcones are popular with their anticancer activities with the several reported mechanisms including inhibition of angiogenesis, inhibition of tubulin polymerization, and induction of apoptosis etc.
Objective: This study was focused on to synthesize of 1-(2,4/2,6-difluorophenyl)-3-(2,3/2,4/2,5/3,4- dimethoxyphenyl)-2-propen-1-ones (1-8) and investigate their cytotoxic properties with possible mechanism of action.
Method: The compounds were synthesized by Claisen-Schmidt condensation. The chemical structures were confirmed by 1H NMR, 13C NMR, DEPT, COSY, HMQC, HMBC, 19F NMR and HRMS. In vitro cytotoxic effects of the compounds against human tumour cell lines [gingival carcinoma (Ca9-22), oral squamous cell carcinoma (HSC-2)] and human normal oral cells [gingival fibroblasts (HGF), periodontal ligament fibroblasts (HPLF)] were evaluated via MTT test.
Results: All compounds had higher cytotoxicity than reference compound 5-Fluorouracil (5-FU). The compounds 3-7 had higher potency selectivity expression values (PSE) than 5-FU and PSE values of the compounds were over 100. All chalcone derivatives seem good candidates for further studies according to very remarkable and high PSE values.
Conclusion: It was clearly demonstrated that compound 7 can induce early apoptosis at a concentration of 10 µM and dose-dependent late apoptosis starting at 10 µM. Compound 7 induced cleavage of the apoptosis marker PARP. The results indicate that new chalcones reported here can promote apoptosis in human tumour cell lines.
Keywords: Chalcone, cytotoxicity, dimethoxy, difluoro, potency selectivity expression, dental cells, PARP.
Anti-Cancer Agents in Medicinal Chemistry
Title:Synthesis and Cytotoxic Activities of Difluoro-Dimethoxy Chalcones
Volume: 17 Issue: 10
Author(s): Cem Yamali, Halise Inci Gul*, Dilan Ozmen Ozgun, Hiroshi Sakagam, Naoki Umemura, Cavit Kazaz and Mustafa Gul
Affiliation:
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum 25240,Turkey
Keywords: Chalcone, cytotoxicity, dimethoxy, difluoro, potency selectivity expression, dental cells, PARP.
Abstract: Background: Although anticancer chemotherapeutics are available in markets, side effects related to the drugs in clinical use lead to researchers to investigate new drug candidates which are more safe, potent and selective than others. Chalcones are popular with their anticancer activities with the several reported mechanisms including inhibition of angiogenesis, inhibition of tubulin polymerization, and induction of apoptosis etc.
Objective: This study was focused on to synthesize of 1-(2,4/2,6-difluorophenyl)-3-(2,3/2,4/2,5/3,4- dimethoxyphenyl)-2-propen-1-ones (1-8) and investigate their cytotoxic properties with possible mechanism of action.
Method: The compounds were synthesized by Claisen-Schmidt condensation. The chemical structures were confirmed by 1H NMR, 13C NMR, DEPT, COSY, HMQC, HMBC, 19F NMR and HRMS. In vitro cytotoxic effects of the compounds against human tumour cell lines [gingival carcinoma (Ca9-22), oral squamous cell carcinoma (HSC-2)] and human normal oral cells [gingival fibroblasts (HGF), periodontal ligament fibroblasts (HPLF)] were evaluated via MTT test.
Results: All compounds had higher cytotoxicity than reference compound 5-Fluorouracil (5-FU). The compounds 3-7 had higher potency selectivity expression values (PSE) than 5-FU and PSE values of the compounds were over 100. All chalcone derivatives seem good candidates for further studies according to very remarkable and high PSE values.
Conclusion: It was clearly demonstrated that compound 7 can induce early apoptosis at a concentration of 10 µM and dose-dependent late apoptosis starting at 10 µM. Compound 7 induced cleavage of the apoptosis marker PARP. The results indicate that new chalcones reported here can promote apoptosis in human tumour cell lines.
Export Options
About this article
Cite this article as:
Yamali Cem , Gul Inci Halise *, Ozgun Ozmen Dilan , Sakagam Hiroshi, Umemura Naoki , Kazaz Cavit and Gul Mustafa, Synthesis and Cytotoxic Activities of Difluoro-Dimethoxy Chalcones, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (10) . https://dx.doi.org/10.2174/1871520617666170327123909
DOI https://dx.doi.org/10.2174/1871520617666170327123909 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Advances in Nanomedicines and Targeted Therapies for Colorectal Cancer
Colorectal cancer remains a significant global health challenge, with high incidence and mortality rates despite advancements in treatment strategies. Conventional therapies often face limitations such as systemic toxicity, drug resistance, and suboptimal targeting. The advent of nanomedicines and innovative drug delivery systems offers new hope for overcoming these challenges and ...read more
Discovery of Lead compounds targeting transcriptional regulation
Transcriptional regulation plays key physiological functions in body growth and development. Transcriptional dysregulation is one of the important biomarkers of tumor genesis and progression, which is involved in regulating tumor cell processes such as cell proliferation, differentiation, and apoptosis. Additionally, it plays a pivotal role in angiogenesis and promotes tumor ...read more
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 that aid in stabilizing chromosomal makeup. The resynthesis of telomeres is supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no telomerase activity in human somatic cells, but the stem cells and germ cells undergo ...read more
Innovative targets in medicinal chemistry
Medicinal chemistry continuously evolves in response to emerging healthcare needs and advancements in scientific understanding. This special issue explores the current landscape of innovative targets in medicinal chemistry, highlighting the quest for novel therapeutic avenues. From traditional drug targets such as enzymes and receptors to emerging targets like protein-protein interactions ...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 Potential Effect of Carvedilol Against Osteoporosis in Ovariectomized Rats
Current Drug Therapy Advanced Oral Drug Delivery Systems for Combating and Preventing Paediatric Periodontal Disease
Letters in Drug Design & Discovery Use of Clays as Nanocarriers of First-Line Tuberculostatic Drugs
Current Drug Delivery New Potential Targets to Modulate Neutrophil Function in Inflammation
Mini-Reviews in Medicinal Chemistry The Janus Face of Cathelicidin in Tumorigenesis
Current Medicinal Chemistry Graphical Abstracts:
Current Topics in Medicinal Chemistry Healing or Not Healing
Current Pharmaceutical Biotechnology The Inflammation Paradigm and Coronary Artery Disease: What Celsus, Virchow and Gene Knock Outs Have Taught Us
Cardiovascular & Hematological Disorders-Drug Targets Graphical Abstracts:
Applied Clinical Research, Clinical Trials and Regulatory Affairs Formulation of Chitosan Nanoparticles Loaded with Metronidazole for the Treatment of Infectious Diseases
Letters in Drug Design & Discovery Extending the Clinical Horizons of Mucosal Bacterial Vaccines: Current Evidence and Future Prospects
Current Drug Targets Molecularly Engineered Polymer-Based Systems in Drug Delivery and Regenerative Medicine
Current Pharmaceutical Design Computational and Experimental Progress on the Structure and Chemical Reactivity of Procyanidins: Their Potential as Metalloproteinases Inhibitors
Current Organic Chemistry Mesenchymal Stem Cells of Dental Origin-Their Potential for Antiinflammatory and Regenerative Actions in Brain and Gut Damage
Current Neuropharmacology Periodontal Film: A Potential Treatment Strategy for Periodontitis
Drug Delivery Letters Proteomic Analysis of Plasma to Reveal the Impact of Short-Term Etanercept Therapy in Pediatric Patients with Enthesitis-Related Arthritis: A Case Report
Combinatorial Chemistry & High Throughput Screening Drug Delivery Systems for Dental Applications
Current Organic Chemistry Immunoadjunctive Therapy against Bacterial Infections Using Herbal Medicines Based on Th17 Cell-mediated Protective Immunity
Current Pharmaceutical Design Intestinal MicrobiOMICS to Define Health and Disease in Human and Mice
Current Pharmaceutical Biotechnology Anticoagulant Therapy for Acute Lung Injury or Pneumonia
Current Drug Targets