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
-
Cancer “Stemness”- Regulating MicroRNAs: Role, Mechanisms and Therapeutic Potential
Current Drug Targets Delivery of Intracellular-Acting Biologics in Pro-Apoptotic Therapies
Current Pharmaceutical Design Activatable Optical Probes for the Detection of Enzymes
Current Organic Synthesis Editorial (Thematic Issue: Microglia - A Therapeutic Target in Neurological Diseases and Disorders)
CNS & Neurological Disorders - Drug Targets An Efficient Light-weight Network for Fast Reconstruction on MR Images
Current Medical Imaging Turning Tumor-Promoting Copper into an Anti-Cancer Weapon via High-Throughput Chemistry
Current Medicinal Chemistry Novel Therapeutic Approaches in Pancreatic Cancer Based on Genomic Alterations
Current Pharmaceutical Design Advanced Micro-Nano-Bio Systems for Future Targeted Therapies
Current Nanoscience Brain Tumor-Related Epilepsy
Current Neuropharmacology Patents and the Development on Polymer based Nanomaterial (PAMAM Dendrimer) for Biomedical Applications
Recent Patents on Biomedical Engineering (Discontinued) Anesthesia Issues in Central Nervous System Disorders
Current Aging Science Kinase Inhibitors with Redox and Anti-inflammatory Activities
Current Topics in Medicinal Chemistry Roles of EGFR, PI3K, AKT, and mTOR in Heavy Metal-Induced Cancer
Current Cancer Drug Targets Current Clinical Applications of In Vivo Magnetic Resonance Spectroscopy and Spectroscopic Imaging
Current Medical Imaging Targeted Delivery of Anti-Inflammatory Agents to Tumors
Current Pharmaceutical Design Liquid Crystal Nanodispersions Enable the Cutaneous Delivery of Photosensitizer for Topical PDT: Fluorescence Microscopy Study of Skin Penetration
Current Nanoscience Recovery of Locomotor Function with Combinatory Drug Treatments Designed to Synergistically Activate Specific Neuronal Networks
Current Medicinal Chemistry Patents Review in siRNA Delivery for Pulmonary Disorders
Recent Patents on Drug Delivery & Formulation PET Molecular Imaging of Hypoxia in Ischemic Stroke: An Update
Current Vascular Pharmacology The Cross-talk between Tristetraprolin and Cytokines in Cancer
Anti-Cancer Agents in Medicinal Chemistry