Abstract
This paper reports the synthesis of a panel of small molecules with arylamides and arylsulfonamides groups and their biological activity in inhibiting nucleotide exchange on human Ras. The design of these molecules was guided by experimental and molecular modelling data previously collected on similar compounds. Aim of this work is the validation of the hypothesis that a phenyl hydroxylamine group linked to a second aromatic moiety generates a pharmacophore capable to interact with Ras and to inhibit its activation. In vitro experiments on purified human Ras clearly show that the presence of an aromatic hydroxylamine and a sulfonamide group in the same molecule is a necessary condition for Ras binding and nucleotide exchange inhibition. The inhibitor potency is lower in molecules in which either the hydroxylamine has been replaced by other functional groups or the sulfonamide has been replaced by an amide. In the case both these moieties, the hydroxylamine and sulfonamide are absent, inactive compounds are obtained.
Keywords: Ras, anticancer agents, computational chemistry, structure-activity relationship
Current Cancer Drug Targets
Title: Structure-Activity Studies on Arylamides and Arysulfonamides Ras Inhibitors
Volume: 10 Issue: 2
Author(s): S. Colombo, A. Palmioli, C. Airoldi, R. Tisi, S. Fantinato, S. Olivieri, L. De Gioia, E. Martegani and F. Peri
Affiliation:
Keywords: Ras, anticancer agents, computational chemistry, structure-activity relationship
Abstract: This paper reports the synthesis of a panel of small molecules with arylamides and arylsulfonamides groups and their biological activity in inhibiting nucleotide exchange on human Ras. The design of these molecules was guided by experimental and molecular modelling data previously collected on similar compounds. Aim of this work is the validation of the hypothesis that a phenyl hydroxylamine group linked to a second aromatic moiety generates a pharmacophore capable to interact with Ras and to inhibit its activation. In vitro experiments on purified human Ras clearly show that the presence of an aromatic hydroxylamine and a sulfonamide group in the same molecule is a necessary condition for Ras binding and nucleotide exchange inhibition. The inhibitor potency is lower in molecules in which either the hydroxylamine has been replaced by other functional groups or the sulfonamide has been replaced by an amide. In the case both these moieties, the hydroxylamine and sulfonamide are absent, inactive compounds are obtained.
Export Options
About this article
Cite this article as:
Colombo S., Palmioli A., Airoldi C., Tisi R., Fantinato S., Olivieri S., De Gioia L., Martegani E. and Peri F., Structure-Activity Studies on Arylamides and Arysulfonamides Ras Inhibitors, Current Cancer Drug Targets 2010; 10 (2) . https://dx.doi.org/10.2174/156800910791054185
DOI https://dx.doi.org/10.2174/156800910791054185 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Expression of Plasma hsa-miR122 in HBV-Related Hepatocellular Carcinoma (HCC) in Vietnamese Patients
MicroRNA The Pattern of Non-AIDS-defining Cancers in the HIV Population: Epidemiology, Risk Factors and Prognosis. A Review
Current HIV Research Regulatable Gene Expression Systems for Gene Therapy
Current Gene Therapy Protein Kinase C-Related Kinase (PKN/PRK). Potential Key-Role for PKN1 in Protection of Hypoxic Neurons
Current Neuropharmacology Radionuclide Based Imaging of Prostate Cancer
Current Topics in Medicinal Chemistry Squalene as Novel Food Factor
Current Pharmaceutical Biotechnology Angiogenesis Inhibitors and Radiation in Multimodality Cancer Therapy: Preclinical and Clinical Studies
Current Angiogenesis (Discontinued) Tomographic Imaging Methods and Gated Technique in Nuclear Cardiology: A Review on Current Status and Future Developments
Recent Patents on Medical Imaging Novel Guanosine Derivatives as Anti-HCV NS5b Polymerase: A QSAR and Molecular Docking Study
Medicinal Chemistry Editorial Review of 2012
Current Radiopharmaceuticals Thyroid Hormones and Cardiovascular System: From Bench to Bedside
Current Drug Therapy The Peri-Viable Baby Down Under - An Australian Perspective on the "Grey Zone" of Viability
Current Pediatric Reviews Effects of Nanosuspension Formulations on Transport, Pharmacokinetics, In Vivo Targeting and Efficacy for Poorly Water-soluble Drugs
Current Pharmaceutical Design Cholesterol-Rich Nanoemulsions (LDE) for Drug Targeting of Cholesteryl-Succinyl- 5-Fluorouracil Conjugate
Current Nanoscience Gold Nanoparticles Conjugated with Glycopeptides for Lectin Detection and Imaging on Cell Surface
Protein & Peptide Letters Menopausal Transition and Chronic Diseases
Current Women`s Health Reviews The Design of G-quadruplex Ligands as Telomerase Inhibitors
Mini-Reviews in Medicinal Chemistry Characterization of Liver- and Cancer-type-Organic Anion Transporting Polypeptide (OATP) 1B3 Messenger RNA Expression in Normal and Cancerous Human Tissues
Drug Metabolism Letters Chemical Instability Determines the Biological Action of the Artemisinins
Current Medicinal Chemistry Radionuclide Antibody-Conjugates, a Targeted Therapy Towards Cancer
Current Radiopharmaceuticals