Abstract
The high mortality rate and lack of effective therapies make lung cancer an ideal target for novel therapeutic agents. The present study was designed to implement a novel chemical synthesis pathway and to determine the biological activities of synthetic makaluvamine analogs in human lung cancer. Seventeen compounds were synthesized and purified, and their chemical structures were elucidated on the basis of physicochemical constants and NMR spectra. Their in vitro activity was determined in human lung cancer cell lines. Based on initial screens, compound Ic was found to be the most potent, and was therefore used as a model for further studies in lung cancer cells. Ic induced both apoptosis and S-phase cell cycle arrest. Furthermore, it activated p53 and induced cleavage of PARP and caspases 8 and 9. Our preclinical data indicate that the makaluvamine analogs are potential therapeutic agents against lung cancer, providing a basis for further development of Ic (and perhaps other analogs) as a novel anti-cancer agent.
Keywords: Makaluvamine, marine alkaloid, lung cancer, apoptosis
Medicinal Chemistry
Title: Synthesis and In Vitro Anti-Lung Cancer Activity of Novel 1, 3, 4, 8- Tetrahydropyrrolo [4, 3, 2-de]quinolin-8(1H)-o ne Alkaloid Analogs
Volume: 5 Issue: 3
Author(s): Dwayaja H. Nadkarni, Feng Wang, Wei Wang, Elizabeth R. Rayburn, Scharri J. Ezell, Srinivasan Murugesan, Sadanandan E. Velu and Ruiwen Zhang
Affiliation:
Keywords: Makaluvamine, marine alkaloid, lung cancer, apoptosis
Abstract: The high mortality rate and lack of effective therapies make lung cancer an ideal target for novel therapeutic agents. The present study was designed to implement a novel chemical synthesis pathway and to determine the biological activities of synthetic makaluvamine analogs in human lung cancer. Seventeen compounds were synthesized and purified, and their chemical structures were elucidated on the basis of physicochemical constants and NMR spectra. Their in vitro activity was determined in human lung cancer cell lines. Based on initial screens, compound Ic was found to be the most potent, and was therefore used as a model for further studies in lung cancer cells. Ic induced both apoptosis and S-phase cell cycle arrest. Furthermore, it activated p53 and induced cleavage of PARP and caspases 8 and 9. Our preclinical data indicate that the makaluvamine analogs are potential therapeutic agents against lung cancer, providing a basis for further development of Ic (and perhaps other analogs) as a novel anti-cancer agent.
Export Options
About this article
Cite this article as:
Nadkarni H. Dwayaja, Wang Feng, Wang Wei, Rayburn R. Elizabeth, Ezell J. Scharri, Murugesan Srinivasan, Velu E. Sadanandan and Zhang Ruiwen, Synthesis and In Vitro Anti-Lung Cancer Activity of Novel 1, 3, 4, 8- Tetrahydropyrrolo [4, 3, 2-de]quinolin-8(1H)-o ne Alkaloid Analogs, Medicinal Chemistry 2009; 5 (3) . https://dx.doi.org/10.2174/157340609788185873
DOI https://dx.doi.org/10.2174/157340609788185873 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
-
Folate Targeted Solid Lipid Nanoparticles of Simvastatin for Enhanced Cytotoxic Effects of Doxorubicin in Chronic Myeloid Leukemia
Current Nanoscience The Biology of the Sodium Iodide Symporter and its Potential for Targeted Gene Delivery
Current Cancer Drug Targets Meet Our Editorial Board Member
Current Medicinal Chemistry Connexins as Precocious Markers and Molecular Targets for Chemical and Pharmacological Agents in Carcinogenesis
Current Medicinal Chemistry Editorial: Overview on microRNAs in Cancer Development and Virus Infection
MicroRNA Innovative Cell Therapy in the Treatment of Serious Adverse Events Related to Both Chemo-Radiotherapy Protocol and Acute Myeloid Leukemia Syndrome: The Infusion of Mesenchymal Stem Cells Post-Treatment Reduces Hematopoietic Toxicity and Promotes Hematopoietic Reconstitution
Current Pharmaceutical Biotechnology Liposome Encapsulated All Trans Retinoic Acid (ATRA) has Enhanced Immunomodulatory and Inflammation Reducing Activities in Mice Model
Anti-Cancer Agents in Medicinal Chemistry Induction of Tumour Cell Senescence: A New Strategy in Anticancer Treatment
Medicinal Chemistry Reviews - Online (Discontinued) Oleamide Derivatives are Prototypical Anti-Metastasis Drugs that Act by Inhibiting Connexin 26
Current Drug Safety An Update on “Selenium Containing Compounds from Poison to Drug Candidates: A Review on the GPx-like Activity”
Current Chemical Biology Aberrant Immunoglobulin Variations as Indicators of Eventual Clonal Changes in Symptomatic Multiple Myeloma Patients' Course
Current Cancer Therapy Reviews Pivotal Role of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 in Inflammatory Pulmonary Diseases
Current Protein & Peptide Science Genetic and Molecular Approaches to the Immunopathogenesis of Multiple Sclerosis: An Update
Current Molecular Medicine The Roles of Sox Family Genes in Sarcoma
Current Drug Targets Nuclear PI-PLCβ1 and Myelodysplastic Syndromes: Genetics and Epigenetics
Current Pharmaceutical Design Bromodomain-Containing Protein 4: A Druggable Target
Current Drug Targets Marine Derived Bioactive Compounds for Breast and Prostate Cancer Treatment: A Review
Current Bioactive Compounds Carotenoids in Photooxidative Stress
Current Nutrition & Food Science Patent Selections:
Recent Patents on Biomarkers The Biological Role of mTOR in the Pathogenesis of Solid Tumors: An Overview
Current Enzyme Inhibition