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 The inhibitor potency is lower in molecules in which either the hydroxylamine has been replaced by other functional groups or the sulfonamide has been replaced by an amide.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 The inhibitor potency is lower in molecules in which either the hydroxylamine has been replaced by other functional groups or the sulfonamide has been replaced by an amide.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
Innovative Cancer Drug Targets: A New Horizon in Oncology
Cancer remains one of the most challenging diseases, with its complexity and adaptability necessitating continuous research efforts into more effective and targeted therapeutic approaches. Recent years have witnessed significant progress in understanding the molecular and genetic basis of cancer, leading to the identification of novel drug targets. These include, but ...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
![](/images/wayfinder.jpg)
- 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
-
Situating Nutri-Ethics at the Junction of Nutrigenomics and Nutriproteomics in Postgenomics Medicine
Current Pharmacogenomics and Personalized Medicine An Efficient Prediction of HPV Genotypes from Partial Coding Sequences by Chaos Game Representation and Fuzzy k-Nearest Neighbor Technique
Current Bioinformatics Oral and Dental Considerations in the Management of Leukemic Children
Applied Clinical Research, Clinical Trials and Regulatory Affairs Breast Cancer: Current Developments in Molecular Approaches to Diagnosis and Treatment
Recent Patents on Anti-Cancer Drug Discovery Breast Cancer Diagnosis System Based on the Fusion of Local Binary and Ternary Patterns from Ultrasound B Mode and Elastography Images
Current Medical Imaging Targeting Protective Catalase of Tumor Cells with Cold Atmospheric Plasma- Activated Medium (PAM)
Anti-Cancer Agents in Medicinal Chemistry Nanoscale Formulations and Diagnostics With Their Recent Trends: A Major Focus of Future Nanotechnology
Current Pharmaceutical Design Plasmid-Mediated Muscle-Targeted Gene Therapy for Circulating Therapeutic Protein Replacement: A Tale of the Tortoise and the Hare?
Current Gene Therapy Plant Natural Products as a Potential Source for Antibacterial Agents: Recent Trends
Anti-Infective Agents in Medicinal Chemistry Molecular Mechanisms of Resistance in Testicular Germ Cell Tumors - clinical Implications
Current Cancer Drug Targets Therapeutic Approaches for Dominant Muscle Diseases: Highlight on Myotonic Dystrophy
Current Gene Therapy Principles of Minimally Invasive Parathyroidectomy
Current Medical Imaging Phosphoregulation of Twist1 Provides a Mechanism of Cell Fate Control
Current Medicinal Chemistry Targeted Therapies in Hepatocellular Carcinoma
Current Medicinal Chemistry Meet Our Editorial Board Member
Current Protein & Peptide Science Advances in the Physiology of GPR55 in the Central Nervous System
Current Neuropharmacology New Technologies in Male Contraception
Current Women`s Health Reviews Inhibitors of Myostatin- and Proteasome-Dependent Signaling for Attenuating Muscle Wasting
Recent Patents on Regenerative Medicine Mesenchymal Stem Cells: Key Actors in Tumor Niche
Current Stem Cell Research & Therapy The Present and Future of Cervical Cancer Screening Programmes in Europe
Current Pharmaceutical Design