Abstract
Glioblastoma Multiforme (GBM) continues to demand improved chemotherapeutic solutions. In order to discover novel chemotherapeutic agents for GBM, we identified novel tetrahydroisoquinoline (THI) analogs as antiglioma agents. The present study reports the design, synthesis and in vitro evaluation of new THI derivatives in four established human glioma cell lines (T98, U87, LN18 and A172). Our structure activity relationship (SAR) studies revealed that the important modification of the carbon linker between the biphenyl and THI ring yielded EDL-360 (12) as a potent antiglioma agent (LN18; IC50: 5.42 ±0.06 μM) and is considered to be our new lead drug candidate for further preclinical studies.
Keywords: Antiglioma activity, EDL-155 analogs, glioblastoma multiforme (GBM), tetrahydroisoquinoline (THI).
Anti-Cancer Agents in Medicinal Chemistry
Title:Synthesis and In Vitro Evaluation of Novel 1,2,3,4-Tetrahydroisoquinoline Derivatives as Potent Antiglioma Agents
Volume: 14 Issue: 3
Author(s): Renukadevi Patil, Amira Hosni-Ahmed, Terreia S. Jones, Shivaputra A. Patil, Likeselam B. Asres, Xiangdi Wang, Ryan C. Yates, Eldon E. Geisert and Duane D. Miller
Affiliation:
Keywords: Antiglioma activity, EDL-155 analogs, glioblastoma multiforme (GBM), tetrahydroisoquinoline (THI).
Abstract: Glioblastoma Multiforme (GBM) continues to demand improved chemotherapeutic solutions. In order to discover novel chemotherapeutic agents for GBM, we identified novel tetrahydroisoquinoline (THI) analogs as antiglioma agents. The present study reports the design, synthesis and in vitro evaluation of new THI derivatives in four established human glioma cell lines (T98, U87, LN18 and A172). Our structure activity relationship (SAR) studies revealed that the important modification of the carbon linker between the biphenyl and THI ring yielded EDL-360 (12) as a potent antiglioma agent (LN18; IC50: 5.42 ±0.06 μM) and is considered to be our new lead drug candidate for further preclinical studies.
Export Options
About this article
Cite this article as:
Patil Renukadevi, Hosni-Ahmed Amira, Jones S. Terreia, Patil A. Shivaputra, Asres B. Likeselam, Wang Xiangdi, Yates C. Ryan, Geisert E. Eldon and Miller D. Duane, Synthesis and In Vitro Evaluation of Novel 1,2,3,4-Tetrahydroisoquinoline Derivatives as Potent Antiglioma Agents, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (3) . https://dx.doi.org/10.2174/18715206113139990328
DOI https://dx.doi.org/10.2174/18715206113139990328 |
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
-
Current Limitations in the Treatment of Parkinson’s and Alzheimer’s Diseases: State-of-the-Art and Future Perspective of Polymeric Carriers
Current Medicinal Chemistry The Novel Functions of cGMP-Specific Phosphodiesterase 5 and its Inhibitors in Carcinoma Cells and Pulmonary/Cardiovascular Vessels
Current Topics in Medicinal Chemistry Calpains: Attractive Targets for the Development of Synthetic Inhibitors
Current Topics in Medicinal Chemistry Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases
Current Pharmaceutical Design TRPV1 Function in Health and Disease
Current Pharmaceutical Biotechnology Heme Oxygenase-1 in Tumor Biology and Therapy
Current Drug Targets Aptamer-Targeted Oligonucleotide Theranostics: A Smarter Approach for Brain Delivery and the Treatment of Neurological Diseases
Current Topics in Medicinal Chemistry Perspectives for Novel Mixed Diruthenium-Organic Drugs as Metallopharmaceuticals in Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Individualized Treatment Planning in Oncology: Role of PET and Radiolabelled Anticancer Drugs in Predicting Tumour Resistance
Current Pharmaceutical Design Targeting ErbB Receptors in High-Grade Glioma
Current Pharmaceutical Design Lipid-based Nanocarriers As An Alternative for Oral Delivery of Poorly Water- Soluble Drugs: Peroral and Mucosal Routes
Current Medicinal Chemistry Circulating Tumor Stem Cells as Biomarkers for Cancer Progression
Recent Patents on Biomarkers Curcumin Nanomedicine: A Road to Cancer Therapeutics
Current Pharmaceutical Design Peptide Phage Display: Opportunities for Development of Personalized Anti-Cancer Strategies
Anti-Cancer Agents in Medicinal Chemistry Microbicidal Tissue Paper Using Green Synthesized Silver Nanoparticles
Current Nanoscience Perspectives in Biomolecular Therapeutic Intervention in Cancer: From the Early to the New Strategies With Type I Interferons
Current Medicinal Chemistry MATra - Magnet Assisted Transfection: Combining Nanotechnology and Magnetic Forces to Improve Intracellular Delivery of Nucleic Acids
Current Pharmaceutical Biotechnology Matrix Metalloproteinase Inhibitors as Prospective Agents for the Prevention and Treatment of Cardiovascular and Neoplastic Diseases
Current Topics in Medicinal Chemistry An Epigenetic Approach to Pancreatic Cancer Treatment: The Prospective Role of Histone Deacetylase Inhibitors
Current Cancer Drug Targets Nerve Growth Factor Receptors and Signaling in Breast Cancer
Current Cancer Drug Targets