Abstract
Background: Colorectal cancer is the third most common form of cancer in both men and women around the world. The chemistry and biological study of heterocyclic compounds have been an interesting area for a long time in pharmaceutical and medicinal chemistry.
Methods: A new synthetic compound, 2-(1,1-dimethyl-1H-benzo[e]indol-2-yl)-3-((2-hydroxyphenyl)amino) acrylaldehyde, abbreviated as DBID, was prepared through the reaction of 2-(diformylmethylidene)-1,1- dimethylbenzo[e]indole with 2-aminophenol. The chemical structure of the synthesized compound was characterized by 1H NMR, 13C NMR and APT-NMR spectroscopy and confirmed by elemental analysis (CHN). The compound was screened for the antiproliferation effect against colorectal cancer cell line, HCT 116 and its possible mechanism of action was elucidated. To determine the IC50 value, the MTT assay was used and its apoptosisinducing effect was investigated.
Results: DBID inhibited the proliferation of HCT 116 cells with an IC50 of 9.32 µg/ml and significantly increased the levels of caspase -8, -9 and -3/7 in the treated cells compared to untreated cells. Apoptosis features in HCT 116 cell was detected in treated cells by using the AO/PI staining that confirmed that the cells had undergone remarkable morphological changes in apoptotic bodies. Furthermore, this changes in expression of caspase -8, -9 and -3 were confirmed by gene and protein quantification using RT-PCR and western blot analysis, respectively.
Conclusion: The current study showed that the DBID compound has demonstrated chemotherapeutic activity which was evidenced by significant increases in the expression and activation of caspase and exploit the apoptotic signaling pathways to trigger cancer cell death.
Keywords: Anticancer activity, colon cancer, new synthetic compound, HCT 116 cell line, pharmacology, heterocyclic compounds.
Current Pharmaceutical Design
Title:Synthesis and Characterization of a New Benzoindole Derivative with Apoptotic Activity Against Colon Cancer Cells
Volume: 23 Issue: 41
Author(s): Fatemeh Hajiaghaalipour*, Fadhil L. Faraj, Elham Bagheri, Hapipah M. Ali, Mahmood Ameen Abdulla and Nazia A. Majid*
Affiliation:
- Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur,Malaysia
- Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur,Malaysia
Keywords: Anticancer activity, colon cancer, new synthetic compound, HCT 116 cell line, pharmacology, heterocyclic compounds.
Abstract: Background: Colorectal cancer is the third most common form of cancer in both men and women around the world. The chemistry and biological study of heterocyclic compounds have been an interesting area for a long time in pharmaceutical and medicinal chemistry.
Methods: A new synthetic compound, 2-(1,1-dimethyl-1H-benzo[e]indol-2-yl)-3-((2-hydroxyphenyl)amino) acrylaldehyde, abbreviated as DBID, was prepared through the reaction of 2-(diformylmethylidene)-1,1- dimethylbenzo[e]indole with 2-aminophenol. The chemical structure of the synthesized compound was characterized by 1H NMR, 13C NMR and APT-NMR spectroscopy and confirmed by elemental analysis (CHN). The compound was screened for the antiproliferation effect against colorectal cancer cell line, HCT 116 and its possible mechanism of action was elucidated. To determine the IC50 value, the MTT assay was used and its apoptosisinducing effect was investigated.
Results: DBID inhibited the proliferation of HCT 116 cells with an IC50 of 9.32 µg/ml and significantly increased the levels of caspase -8, -9 and -3/7 in the treated cells compared to untreated cells. Apoptosis features in HCT 116 cell was detected in treated cells by using the AO/PI staining that confirmed that the cells had undergone remarkable morphological changes in apoptotic bodies. Furthermore, this changes in expression of caspase -8, -9 and -3 were confirmed by gene and protein quantification using RT-PCR and western blot analysis, respectively.
Conclusion: The current study showed that the DBID compound has demonstrated chemotherapeutic activity which was evidenced by significant increases in the expression and activation of caspase and exploit the apoptotic signaling pathways to trigger cancer cell death.
Export Options
About this article
Cite this article as:
Hajiaghaalipour Fatemeh *, Faraj L. Fadhil , Bagheri Elham , Ali M. Hapipah , Abdulla Ameen Mahmood and Majid A. Nazia*, Synthesis and Characterization of a New Benzoindole Derivative with Apoptotic Activity Against Colon Cancer Cells, Current Pharmaceutical Design 2017; 23 (41) . https://dx.doi.org/10.2174/1381612823666170321093345
DOI https://dx.doi.org/10.2174/1381612823666170321093345 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Targeting Tumor Lymphangiogenesis: An Update
Current Medicinal Chemistry Novel Therapies Against Aggressive and Recurrent Epithelial Cancers by Molecular Targeting Tumor- and Metastasis-Initiating Cells and Their Progenies
Anti-Cancer Agents in Medicinal Chemistry Nitric Oxide and Cancer Therapy: The Emperor has NO Clothes
Current Pharmaceutical Design Light-at-Night-Induced Circadian Disruption, Cancer and Aging
Current Aging Science Endoscopic Microscopy Using Optical Coherence Tomography
Current Medical Imaging Patent Selections:
Recent Patents on Anti-Cancer Drug Discovery Synthesis of Silica Based Nanoparticles Against the Proliferation of Human Prostate Cancer
Anti-Cancer Agents in Medicinal Chemistry Role of Phase II Drug Metabolizing Enzymes in Cancer Chemoprevention
Current Drug Metabolism Pharmacogenetics of Phase I and Phase II Drug Metabolism
Current Pharmaceutical Design Mycotoxins Levels in Human Milk: A Menace to Infants and Children Health
Current Nutrition & Food Science DNA Intercalators in Cancer Therapy: Organic and Inorganic Drugs and Their Spectroscopic Tools of Analysis
Mini-Reviews in Medicinal Chemistry Targeting Matrix Metalloproteinases in Inflammatory Conditions
Current Drug Targets Recent Progress in the Development of Anticancer Agents
Current Medicinal Chemistry - Anti-Cancer Agents Treatment for Cancer Patients with Oral Mucositis: Assessment Based on the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer in International Society of Oral Oncology (MASCC/ISOO) in 2013 and Proposal of Possible Novel Treatment with a Japanese Herbal Medicine
Current Pharmaceutical Design Cancer Kinases and its Novel Inhibitors: Past, Present and Future Challenges
Current Drug Targets Epi-Drugs and Epi-miRs: Moving Beyond Current Cancer Therapies
Current Cancer Drug Targets CD26: A Multi-Purpose Pharmacological Target
Current Clinical Pharmacology Development of a Novel Reporter Gene Vector for Cell Based Angiogenic Studies
Combinatorial Chemistry & High Throughput Screening Generation of Anti-Colorectal Cancer Fab Phage Display Libraries With a High Percentage of Diverse Antigen-Reactive Clones
Combinatorial Chemistry & High Throughput Screening Prevention of Non-communicable Diseases by Balanced Nutrition: Population- specific Effective Public Health Approaches in Developing Countries
Current Diabetes Reviews