Abstract
All chemotherapeutic agents currently in use have a narrow window of therapeutic index of 1 to 1.2. Camptothecin ester compounds are reported to have a wider therapeutic index when being used to treat human xenografts in nude mice. As a continuous effort in searching for better chemotherapeutic agents for treating cancers, new haloalkyl camptothecin and 9-nitrocamptothecin ester derivatives 2a-b and 3a-d were prepared by respective acylation of camptothecin 1a and 9-nitrocamptothecin 1b with the corresponding acylating agents. These new derivatives were tested in vitro against 8 human cancer cell lines using 7 different concentrations ranging from 5 to 300 nM and also in vivo against various types of human tumor xenografts grown in nude mice. Most of these new compounds started showing inhibitory effects on the growth of 8 cancer cell lines at concentration of 80 nM and achieved greater than 70% inhibitions against these cell lines when the concentration increased to 300 nM. Compound 2a and 3a showed good activity against human tumor xenografts in nude mice. Compared to mother compound camptothecin, 3a was much less toxic in mice with a better therapeutic index, having the potential to be further developed as a safer treatment for cancers.
Keywords: Anticancer activity, Camptothecin esters, Esterification, Human tumor xenografts, Nude mice, Prodrugs, Therapeutic index, Topoisomerase 1, Toxicity, cytotoxic alkaloidal compound.
Anti-Cancer Agents in Medicinal Chemistry
Title:Anticancer Activity of New Haloalkyl Camptothecin Esters against Human Cancer Cell Lines and Human Tumor Xenografts Grown in Nude Mice
Volume: 12 Issue: 7
Author(s): Zhisong Cao, John Mendoza, Anthony Kozielski, Xing Liu, Albert DeJesus, Yang Wang, Chang-Guo Zhan, Dana Vardeman and Beppino Giovanella
Affiliation:
Keywords: Anticancer activity, Camptothecin esters, Esterification, Human tumor xenografts, Nude mice, Prodrugs, Therapeutic index, Topoisomerase 1, Toxicity, cytotoxic alkaloidal compound.
Abstract: All chemotherapeutic agents currently in use have a narrow window of therapeutic index of 1 to 1.2. Camptothecin ester compounds are reported to have a wider therapeutic index when being used to treat human xenografts in nude mice. As a continuous effort in searching for better chemotherapeutic agents for treating cancers, new haloalkyl camptothecin and 9-nitrocamptothecin ester derivatives 2a-b and 3a-d were prepared by respective acylation of camptothecin 1a and 9-nitrocamptothecin 1b with the corresponding acylating agents. These new derivatives were tested in vitro against 8 human cancer cell lines using 7 different concentrations ranging from 5 to 300 nM and also in vivo against various types of human tumor xenografts grown in nude mice. Most of these new compounds started showing inhibitory effects on the growth of 8 cancer cell lines at concentration of 80 nM and achieved greater than 70% inhibitions against these cell lines when the concentration increased to 300 nM. Compound 2a and 3a showed good activity against human tumor xenografts in nude mice. Compared to mother compound camptothecin, 3a was much less toxic in mice with a better therapeutic index, having the potential to be further developed as a safer treatment for cancers.
Export Options
About this article
Cite this article as:
Cao Zhisong, Mendoza John, Kozielski Anthony, Liu Xing, DeJesus Albert, Wang Yang, Zhan Chang-Guo, Vardeman Dana and Giovanella Beppino, Anticancer Activity of New Haloalkyl Camptothecin Esters against Human Cancer Cell Lines and Human Tumor Xenografts Grown in Nude Mice, Anti-Cancer Agents in Medicinal Chemistry 2012; 12 (7) . https://dx.doi.org/10.2174/187152012802650219
DOI https://dx.doi.org/10.2174/187152012802650219 |
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
-
Cannabinoid Receptor Activation and the Endocannabinoid System in the Gastrointestinal Tract
Current Neuropharmacology Estrogens and Colorectal Cancer
Current Drug Targets - Immune, Endocrine & Metabolic Disorders COX-2: Friend or Foe?
Current Pharmaceutical Design Propitious Profile of Peppery Piperine
Current Molecular Pharmacology Azoles as Effective Antifungal Agents: Trends, Scope and Relevance
The Natural Products Journal HCV-Related Transformation and New Therapeutic Strategies: An Update
Current Cancer Therapy Reviews Synthesis and Cytotoxicity Assessment of Novel 7-O- and 14-O-Derivatives of Glaucocalyxin A
Anti-Cancer Agents in Medicinal Chemistry COX-2 Inhibitors and Cardiovascular Events: Deja Vu Du Jour
Vascular Disease Prevention (Discontinued) Pathogenesis of and Therapeutic Strategies to Ameliorate the Transthyretin Amyloidoses
Current Pharmaceutical Design Intelligent Drug Delivery Systems Based on Modified Chitosan Nanoparticles
Letters in Organic Chemistry VEGF and HIF in Renal Cell Carcinogenesis
Recent Patents on Biomarkers Anesthetic and Adjunctive Drugs for Fast-Track Surgery
Current Drug Targets Dietary Phytochemicals in Chemoprevention of Cancer: An Update
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) EGFR-Targeted Therapy in Malignant Glioma: Novel Aspects and Mechanisms of Drug Resistance
Current Molecular Pharmacology Sam68 Promotes the Progression of Human Breast Cancer through inducing Activation of EphA3
Current Cancer Drug Targets Peptide Aptamers: Development and Applications
Current Topics in Medicinal Chemistry A Survey on Machine Learning Based Medical Assistive Systems in Current Oncological Sciences
Current Medical Imaging MicroRNAs and Bone Regeneration
Current Genomics Prevention of Cancer in the Upper Gastrointestinal Tract with COX-Inhibition. Still an Option?
Current Pharmaceutical Design Novel Anti-inflammatory Drugs from Marine Microbes
The Natural Products Journal