Topoisomerase inhibitors as anticancer agents: a patent update
- PMID: 23611704
- DOI: 10.1517/13543776.2013.790958
Topoisomerase inhibitors as anticancer agents: a patent update
Abstract
Introduction: Topoisomerases (topos) are nuclear enzymes that resolve topological problems associated with DNA during various genetic processes. The essential role of topos in vital processes of the cell, their elevated level in solid tumors and cell death due to their inhibition make topos inhibitors as a potent class of antineoplastic agents.
Areas covered: This review specifically summarizes patents embracing topo I, topo I and II inhibitors. The review covers topos inhibitors which are structurally close to camptothecin (CPT), natural products such as lamellarins and synthetic trisubstituted pyridines. It largely focuses on chemical entities developed by systematic structure-activity relationship (SAR) studies of natural benzo[c]phenanthridine (nitidine) and synthetic protoberberine (coralyne) established as antineoplastic agents targeting topo(s). In addition, indenoisoquinolines and evodiamines initially discovered through COMPARE analysis and receptor-based virtual screening (VS) respectively have been discussed.
Expert opinion: Along with conventional techniques, computer-aided VS, molecular modeling and docking studies have been applied for drug design, discovery and development. Computer-aided tools provide a rational way to explain pharmacological activities of topos inhibitors under study. Comparative study of crystal structures of topo I/II-DNA-drug ternary complex and use of appropriate pharmacological screening methods will lead to potential anticancer drugs in the coming days.
Similar articles
-
Design, synthesis and systematic evaluation of cytotoxic 3-heteroarylisoquinolinamines as topoisomerases inhibitors.Eur J Med Chem. 2014 Jul 23;82:181-94. doi: 10.1016/j.ejmech.2014.05.047. Epub 2014 May 21. Eur J Med Chem. 2014. PMID: 24904965
-
Recent advances in the development of dual topoisomerase I and II inhibitors as anticancer drugs.Curr Med Chem. 2010;17(35):4270-90. doi: 10.2174/092986710793361252. Curr Med Chem. 2010. PMID: 20939813 Review.
-
Identification of topoisomerase I as the cytotoxic target of the protoberberine alkaloid coralyne.Cancer Res. 1996 Jun 15;56(12):2795-800. Cancer Res. 1996. PMID: 8665516
-
Synthesis and biological evaluation of benzo[a]phenazine derivatives as a dual inhibitor of topoisomerase I and II.Org Biomol Chem. 2013 Jun 28;11(24):3989-4005. doi: 10.1039/c3ob40325d. Org Biomol Chem. 2013. PMID: 23657605
-
Natural Products as Anti-Cancerous Therapeutic Molecules Targeted towards Topoisomerases.Curr Protein Pept Sci. 2020;21(11):1103-1142. doi: 10.2174/1389203721666200918152511. Curr Protein Pept Sci. 2020. PMID: 32951576 Review.
Cited by
-
Tackling the Cytotoxic Effect of a Marine Polycyclic Quinone-Type Metabolite: Halenaquinone Induces Molt 4 Cells Apoptosis via Oxidative Stress Combined with the Inhibition of HDAC and Topoisomerase Activities.Mar Drugs. 2015 May 20;13(5):3132-53. doi: 10.3390/md13053132. Mar Drugs. 2015. PMID: 26006712 Free PMC article.
-
DNA Damage-Inducing Anticancer Therapies: From Global to Precision Damage.Cancers (Basel). 2020 Jul 28;12(8):2098. doi: 10.3390/cancers12082098. Cancers (Basel). 2020. PMID: 32731592 Free PMC article. Review.
-
Cellular Senescence as a Brake or Accelerator for Oncogenic Transformation and Role in Lymphatic Metastasis.Int J Mol Sci. 2023 Feb 2;24(3):2877. doi: 10.3390/ijms24032877. Int J Mol Sci. 2023. PMID: 36769195 Free PMC article. Review.
-
Dual Topoisomerase I/II Inhibition-Induced Apoptosis and Necro-Apoptosis in Cancer Cells by a Novel Ciprofloxacin Derivative via RIPK1/RIPK3/MLKL Activation.Molecules. 2022 Nov 17;27(22):7993. doi: 10.3390/molecules27227993. Molecules. 2022. PMID: 36432094 Free PMC article.
-
Assessment of DNA Topoisomerase I Unwinding Activity, Radical Scavenging Capacity, and Inhibition of Breast Cancer Cell Viability of N-alkyl-acridones and N,N'-dialkyl-9,9'-biacridylidenes.Biomolecules. 2019 May 8;9(5):177. doi: 10.3390/biom9050177. Biomolecules. 2019. PMID: 31072044 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous
