Abstract
As a continuation of our efforts to develop the benzimidazole-PBD conjugates as potential anticancer agents, a series of heteroaryl substituted benzimidazole linked PBD conjugates has been synthesized and evaluated for their anticancer potential in 60 human cancer cell lines. Most of the compounds exhibited promising anticancer activity and interestingly, compounds 4c and 4d displayed significant activity in most of the cell lines tested. Whereas, compound 4e showed selectivity in renal cancer cells with GI50 values of < 10 and 70 nM against RXF 393 and UO-31 cell lines, respectively. Further, these compounds also showed significant DNA-binding affinity by thermal denaturation study using duplex form of calf thymus (CT) DNA.
Keywords: Pyrrolobenzodiazepine, benzimidazoles, cytotoxicity, DNA-binding affinity.
Medicinal Chemistry
Title:Synthesis, DNA Binding Ability and Anticancer Activity of 2-heteroaryl Substituted Benzimidazoles Linked Pyrrolo[2,1-c][1,4]benzodiazepine Conjugates
Volume: 9 Issue: 5
Author(s): Ahmed Kamal, Praveen Kumar Pogula, Mohammed Naseer Ahmed Khan, Bobburi Naga Seshadri and Kokkonda Sreekanth
Affiliation:
Keywords: Pyrrolobenzodiazepine, benzimidazoles, cytotoxicity, DNA-binding affinity.
Abstract: As a continuation of our efforts to develop the benzimidazole-PBD conjugates as potential anticancer agents, a series of heteroaryl substituted benzimidazole linked PBD conjugates has been synthesized and evaluated for their anticancer potential in 60 human cancer cell lines. Most of the compounds exhibited promising anticancer activity and interestingly, compounds 4c and 4d displayed significant activity in most of the cell lines tested. Whereas, compound 4e showed selectivity in renal cancer cells with GI50 values of < 10 and 70 nM against RXF 393 and UO-31 cell lines, respectively. Further, these compounds also showed significant DNA-binding affinity by thermal denaturation study using duplex form of calf thymus (CT) DNA.
Export Options
About this article
Cite this article as:
Kamal Ahmed, Pogula Kumar Praveen, Khan Naseer Ahmed Mohammed, Seshadri Naga Bobburi and Sreekanth Kokkonda, Synthesis, DNA Binding Ability and Anticancer Activity of 2-heteroaryl Substituted Benzimidazoles Linked Pyrrolo[2,1-c][1,4]benzodiazepine Conjugates, Medicinal Chemistry 2013; 9 (5) . https://dx.doi.org/10.2174/1573406411309050004
DOI https://dx.doi.org/10.2174/1573406411309050004 |
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
-
Design, Synthesis and Biochemical Evaluation of Estrogen Receptor Ligand Conjugates as Tumour Targeting Agents
Letters in Drug Design & Discovery H3K4 Methylation Status and Lysine Specific Methyltransferase KMT2C Expression Correlate with Prognosis in Lung Adenocarcinoma
Current Molecular Pharmacology Histone Deacetylase Inhibitors In Inflammatory Disease
Current Topics in Medicinal Chemistry Cyclin-Dependent Kinase Inhibitors as Anticancer Drugs
Current Drug Targets Anti-Apoptotic Mechanisms of Drug Resistance in Cancer
Current Cancer Drug Targets Potential Beneficial Effects of Garlic in Oncohematology
Mini-Reviews in Medicinal Chemistry Melatonin, A Natural Programmed Cell Death Inducer in Cancer
Current Medicinal Chemistry Glioma Stem Cell Maintenance: The Role of the Microenvironment
Current Pharmaceutical Design Strategies for the Design of Potent and Selective Kinase Inhibitors
Current Pharmaceutical Design The Chlorophyll Catabolite Pheophorbide a as a Photosensitizer for the Photodynamic Therapy
Current Medicinal Chemistry Prodrugs of Non-steroidal Anti-inflammatory Drugs (NSAIDs): A Long March Towards Synthesis of Safer NSAIDs
Mini-Reviews in Medicinal Chemistry CDK-associated Cullin 1 Promotes Cell Proliferation and Inhibits Cell Apoptosis in Human Glioblastoma
Current Cancer Drug Targets Advances in the Researches on the Biological Activities and Inhibitors of Phosphatidylinositol 3-kinase
Anti-Cancer Agents in Medicinal Chemistry Significance of Prion and Prion-Like Proteins in Cancer Development, Progression and Multi-Drug Resistance
Current Cancer Drug Targets Acute Graft-Versus-Host Disease-Challenge for a Broader Application of Allogeneic Hematopoietic Cell Transplantation
Current Stem Cell Research & Therapy T Cell Suicide Gene Therapy to Aid Haematopoietic Stem Cell Transplantation
Current Gene Therapy HSP90 Inhibitors: Multi-Targeted Antitumor Effects and Novel Combinatorial Therapeutic Approaches in Cancer Therapy
Current Medicinal Chemistry Small-molecule Inhibitors of Epigenetic Mutations as Compelling Drugtargets for Myelodysplastic Syndromes
Current Cancer Drug Targets Pleiotropic Effect of Mahanine and Girinimbine Analogs: Anticancer Mechanism and its Therapeutic Versatility
Anti-Cancer Agents in Medicinal Chemistry Approaches to Quantification of RNA Targets by PCR Based Techniques
Current Genomics