Abstract
Microtubules are involved in many critical cellular processes including cell division, cell shape maintenance, vesicle transportation and motility regulation. Disruption of tubulin dynamics is a well-validated cancer drug target with several FDA approved, highly efficacious tubulin inhibitors targeting the taxane or the vinca binding sites. Despite the tremendous successes for these clinical tubulin inhibitors, their limitations are also apparent, particularly in the development of transporter mediated drug resistance. While currently there are no FDA approved inhibitors targeting the colchicine binding site in tubulin, extensive preclinical studies have suggested that colchicine binding site inhibitors (CBSIs) have significantly less susceptibility to transporter medicated drug resistance. The presence of one or more heterocyclic moieties is often critical for the antiproliferative activities for most of these CBSIs. This article aims to review the structures and antiproliferative activities of most recently developed heterocyclic CBSIs from 2013 to present. We focus this review on compounds that are designed based on the CA-4, chalcone and PTOX scaffolds which are well established to interact with the colchicine binding site in tubulin.
Keywords: Heterocyclic tubulin inhibitors, colchicine binding site, CA-4 analogs, chalcone analogs, PTOX analogs.
Anti-Cancer Agents in Medicinal Chemistry
Title:Recent Advances in Heterocyclic Tubulin Inhibitors Targeting the Colchicine Binding Site
Volume: 16 Issue: 10
Author(s): Xiaoxin Wu, Qinghui Wang and Wei Li
Affiliation:
Keywords: Heterocyclic tubulin inhibitors, colchicine binding site, CA-4 analogs, chalcone analogs, PTOX analogs.
Abstract: Microtubules are involved in many critical cellular processes including cell division, cell shape maintenance, vesicle transportation and motility regulation. Disruption of tubulin dynamics is a well-validated cancer drug target with several FDA approved, highly efficacious tubulin inhibitors targeting the taxane or the vinca binding sites. Despite the tremendous successes for these clinical tubulin inhibitors, their limitations are also apparent, particularly in the development of transporter mediated drug resistance. While currently there are no FDA approved inhibitors targeting the colchicine binding site in tubulin, extensive preclinical studies have suggested that colchicine binding site inhibitors (CBSIs) have significantly less susceptibility to transporter medicated drug resistance. The presence of one or more heterocyclic moieties is often critical for the antiproliferative activities for most of these CBSIs. This article aims to review the structures and antiproliferative activities of most recently developed heterocyclic CBSIs from 2013 to present. We focus this review on compounds that are designed based on the CA-4, chalcone and PTOX scaffolds which are well established to interact with the colchicine binding site in tubulin.
Export Options
About this article
Cite this article as:
Wu Xiaoxin, Wang Qinghui and Li Wei, Recent Advances in Heterocyclic Tubulin Inhibitors Targeting the Colchicine Binding Site, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (10) . https://dx.doi.org/10.2174/1871520616666160219161921
DOI https://dx.doi.org/10.2174/1871520616666160219161921 |
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
-
Nitric Oxide Control of Proliferation in Nerve Cells and in Tumor Cells of Nervous Origin
Current Pharmaceutical Design The Pathophysiology of Heme in the Brain
Current Alzheimer Research Telomere Maintenance as Therapeutic Target in Embryonal Tumours
Anti-Cancer Agents in Medicinal Chemistry Indoleamine 2,3-Dioxygenase in Immune Suppression and Cancer
Current Cancer Drug Targets Cyclin Dependent Kinase 1 Inhibitors: A Review of Recent Progress
Current Medicinal Chemistry Immunomodulatory Effects of <i>Allium sativum</i> L. and its Constituents against Viral Infections and Metabolic Diseases
Current Topics in Medicinal Chemistry Prospects for Rational Development of Pharmacological Gap Junction Channel Blockers
Current Drug Targets Cyclin-Dependent Kinase Inhibition by Flavoalkaloids
Mini-Reviews in Medicinal Chemistry Signal Transduction via Cannabinoid Receptors
CNS & Neurological Disorders - Drug Targets Insulin-Like Growth Factor 1 Receptor Targeted Therapeutics: Novel Compounds and Novel Treatment Strategies for Cancer Medicine
Recent Patents on Anti-Cancer Drug Discovery Identification of Novel Key Targets and Candidate Drugs in Oral Squamous Cell Carcinoma
Current Bioinformatics Modulators of Voltage-Dependent Calcium Channels for the Treatment of Nervous System Diseases
Recent Patents on CNS Drug Discovery (Discontinued) Machine Learning Based Pattern Recognition Applied to Microarray Data
Combinatorial Chemistry & High Throughput Screening Clostridial Neurotoxins: Mode of Substrate Recognition and Novel Therapy Development
Current Protein & Peptide Science Inhibitors of the Ubiquitin-Proteasome System and the Cell Death Machinery: How Many Pathways are Activated?
Current Molecular Pharmacology LRRC4 Inhibits Glioma Cell Growth and Invasion Through a miR-185- Dependent Pathway
Current Cancer Drug Targets Long Non-coding RNA HOTAIR Promotes Parkinson's Disease Induced by MPTP Through up-regulating the Expression of LRRK2
Current Neurovascular Research Liposome-linear polyethyleneimine-DNA Nanocomplexes for Gene Delivery: Preparation, Characterization and In Vitro Transfection Activity
Current Nanoscience Platelet-Activating Factor (PAF) Antagonists Attenuate Inflammatory- Based Pain: Potential Cellular and Anatomical Sites of PAF Action
Central Nervous System Agents in Medicinal Chemistry Passive and Active Tumour Targeting with Nanocarriers
Current Drug Discovery Technologies