Abstract
Anticancer drugs are often nonselective antiproliferative agents (cytotoxins) that preferentially kill dividing cells by attacking their DNA at some level. The lack of selectivity results in significant toxicity to noncancerous proliferating cells. These toxicities along with drug resistance exhibited by the solid tumors are major therapy limiting factors that result into poor prognosis for patients. Prodrug and conjugate design involves the synthesis of inactive drug derivatives that are converted to an active form inside the body and preferably at the site of action. Classical prodrug and conjugate design have focused on the development of prodrugs that can overcome physicochemical (e.g., solubility, chemical instability) or biopharmaceutical problems (e.g., bioavailability, toxicity) associated with common anticancer drugs. The recent targeted prodrug and conjugate design, on the other hand, hinge on the selective delivery of anticancer agents to tumor tissues thereby avoiding their cytotoxic effects on noncancerous cells. Targeting strategies have attempted to take advantage of low extracellular pH, elevated enzymes in tumor tissues, the hypoxic environment inside the tumor core, and tumor-specific antigens expressed on tumor cell surfaces. The present review highlights recent trends in prodrug and conjugate rationale and design for cancer treatment. The various approaches that are currently being explored are critically analyzed and a comparative account of the advantages and disadvantages associated with each approach is presented.
Keywords: Prodrugs, conjugates, targeted design, nanotechnology, anticancer
Current Medicinal Chemistry
Title: Recent Trends in Targeted Anticancer Prodrug and Conjugate Design
Volume: 15 Issue: 18
Author(s): Yashveer Singh, Matthew Palombo and Patrick J. Sinko
Affiliation:
Keywords: Prodrugs, conjugates, targeted design, nanotechnology, anticancer
Abstract: Anticancer drugs are often nonselective antiproliferative agents (cytotoxins) that preferentially kill dividing cells by attacking their DNA at some level. The lack of selectivity results in significant toxicity to noncancerous proliferating cells. These toxicities along with drug resistance exhibited by the solid tumors are major therapy limiting factors that result into poor prognosis for patients. Prodrug and conjugate design involves the synthesis of inactive drug derivatives that are converted to an active form inside the body and preferably at the site of action. Classical prodrug and conjugate design have focused on the development of prodrugs that can overcome physicochemical (e.g., solubility, chemical instability) or biopharmaceutical problems (e.g., bioavailability, toxicity) associated with common anticancer drugs. The recent targeted prodrug and conjugate design, on the other hand, hinge on the selective delivery of anticancer agents to tumor tissues thereby avoiding their cytotoxic effects on noncancerous cells. Targeting strategies have attempted to take advantage of low extracellular pH, elevated enzymes in tumor tissues, the hypoxic environment inside the tumor core, and tumor-specific antigens expressed on tumor cell surfaces. The present review highlights recent trends in prodrug and conjugate rationale and design for cancer treatment. The various approaches that are currently being explored are critically analyzed and a comparative account of the advantages and disadvantages associated with each approach is presented.
Export Options
About this article
Cite this article as:
Singh Yashveer, Palombo Matthew and Sinko J. Patrick, Recent Trends in Targeted Anticancer Prodrug and Conjugate Design, Current Medicinal Chemistry 2008; 15 (18) . https://dx.doi.org/10.2174/092986708785132997
DOI https://dx.doi.org/10.2174/092986708785132997 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
The Potential Role of Peritumoral Apparent Diffusion Coefficient Evaluation in Differentiating Glioblastoma and Solitary Metastatic Lesions of the Brain
Current Medical Imaging A Role for the Inflammatory Mediators Cox-2 and Metalloproteinases in Cancer Stemness
Anti-Cancer Agents in Medicinal Chemistry Recent Advances in Efficacy of using Doxorubicin Gold Nanoparticles for Chemo-, Radio-, Photothermal, and Photodynamic Therapy
Current Drug Delivery Meet Our Associate Editorial Board Member
Current Drug Delivery Mechanisms of Resistance to Photodynamic Therapy
Current Medicinal Chemistry Gender Disparity in Pediatric Diseases
Current Molecular Medicine Erythropoietin: Cytoprotection in Vascular and Neuronal Cells
Current Drug Targets - Cardiovascular & Hematological Disorders iRGD Co-Administration with Paclitaxel-Loaded PLGA Nanoparticles Enhance Targeting and Antitumor Effect in Colorectal Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Exploiting Apoptosis Pathways for the Treatment of Pancreatic Cancer
Current Signal Transduction Therapy Adenovirus-mediated Transgene-engineered Dendritic Cell Vaccine of Cancer
Current Gene Therapy Marine Natural Products with High Anticancer Activities
Current Medicinal Chemistry Natural Compounds as Inhibitors of SARS-CoV-2 Main Protease (3CLpro): A Molecular Docking and Simulation Approach to Combat COVID-19
Current Pharmaceutical Design Amyloid Beta Peptide 1-40 Stimulates the Na+ / Ca2+ Exchange Activity of SNCX
Current Neurovascular Research Inflammation and Antiangiogenesis in Cancer
Current Medicinal Chemistry Review of Clinic Trials: Agents Targeting c-Met
Reviews on Recent Clinical Trials Induction of Antitumor Immune Responses with Recombinant Lentivector: Role of Skin Derived DCs
Current Cancer Therapy Reviews Molecular Biology, Pharmacology and Functional Role of the Plasma Membrane Dopamine Transporter
CNS & Neurological Disorders - Drug Targets Oncolytic HSV-1 Virotherapy: Clinical Experience and Opportunities for Progress
Current Pharmaceutical Biotechnology Phosphatidylinositol 3-Kinase Isoforms as Novel Drug Targets
Current Drug Targets Graphene and Graphene Oxide as a Docking Station for Modern Drug Delivery System
Current Drug Delivery