Abstract
Bladder cancer (BLC) is a very dangerous and common disease which is characterized by an uncontrolled growth of the urinary bladder cells. In the field of chemotherapy, many compounds have been synthesized and evaluated as anti-BLC agents. The future design of more potent anti-BLC drugs depends on a rigorous and rational discovery, where the computer-aided design (CADD) methodologies should play a very important role. However, until now, there is no CADD methodology able to predict anti-BLC activity of compounds versus different BLC cell lines. We report in this work the first unified approach by exploring Quantitative- Structure Activity Relationship (QSAR) studies using a large and heterogeneous database of compounds. Here, we constructed two multi-target (mt) QSAR models for the classification of compounds as anti-BLC agents against four BLC cell lines. The first model was based on linear discriminant analysis (mt-QSAR-LDA) employing fragment-based descriptors while the second model was obtained using artificial neural networks (mt-QSAR-ANN) with global 2D descriptors. Both models correctly classified more than 90% of active and inactive compounds in training and prediction sets. We also extracted different substructural patterns which could be responsible for the activity/inactivity of molecules against BLC and we suggested new molecular entities as possible potent and versatile anti-BLC agents.
Keywords: Artificial neural networks, bladder cancer, fragments, in silico design, linear discriminant analysis, molecular descriptors, mt- QSAR, quantitative contributions.
Anti-Cancer Agents in Medicinal Chemistry
Title:Unified Multi-target Approach for the Rational in silico Design of Anti-bladder Cancer Agents
Volume: 13 Issue: 5
Author(s): Alejandro Speck- Planche, Valeria V. Kleandrova, Feng Luan and M. N. D. S. Cordeiro
Affiliation:
Keywords: Artificial neural networks, bladder cancer, fragments, in silico design, linear discriminant analysis, molecular descriptors, mt- QSAR, quantitative contributions.
Abstract: Bladder cancer (BLC) is a very dangerous and common disease which is characterized by an uncontrolled growth of the urinary bladder cells. In the field of chemotherapy, many compounds have been synthesized and evaluated as anti-BLC agents. The future design of more potent anti-BLC drugs depends on a rigorous and rational discovery, where the computer-aided design (CADD) methodologies should play a very important role. However, until now, there is no CADD methodology able to predict anti-BLC activity of compounds versus different BLC cell lines. We report in this work the first unified approach by exploring Quantitative- Structure Activity Relationship (QSAR) studies using a large and heterogeneous database of compounds. Here, we constructed two multi-target (mt) QSAR models for the classification of compounds as anti-BLC agents against four BLC cell lines. The first model was based on linear discriminant analysis (mt-QSAR-LDA) employing fragment-based descriptors while the second model was obtained using artificial neural networks (mt-QSAR-ANN) with global 2D descriptors. Both models correctly classified more than 90% of active and inactive compounds in training and prediction sets. We also extracted different substructural patterns which could be responsible for the activity/inactivity of molecules against BLC and we suggested new molecular entities as possible potent and versatile anti-BLC agents.
Export Options
About this article
Cite this article as:
Planche Alejandro Speck-, Kleandrova Valeria V., Luan Feng and Cordeiro M. N. D. S., Unified Multi-target Approach for the Rational in silico Design of Anti-bladder Cancer Agents, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (5) . https://dx.doi.org/10.2174/1871520611313050013
DOI https://dx.doi.org/10.2174/1871520611313050013 |
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
-
Cellular Therapy for Treatment of Stress Urinary Incontinence
Current Stem Cell Research & Therapy Aspirin Use on Incidence and Mortality of Gastrointestinal Cancers: Current State of Epidemiological Evidence
Current Pharmaceutical Design The Beneficial Effects of QIAPI 1<sup>®</sup> against Pentavalent Arsenic-Induced Lung Toxicity: A Hypothetical Model for SARS CoV2-I nduced Lung Toxicity
Current Pharmaceutical Biotechnology Soy Saponins and the Anticancer Effects of Soybeans and Soy-Based Foods
Current Medicinal Chemistry - Anti-Cancer Agents Synthesis and Anti-cancer Activities of Apigenin Derivatives
Medicinal Chemistry Estrogen and Female Lower Urinary Tract Dysfunction
Current Women`s Health Reviews Sulfotransferase 1A1 as a Biomarker for Susceptibility to Carcinogenesis: From Molecular Genetics to the Role of Dietary Flavonoids
Current Drug Metabolism Drug-Eluting Stents: Present and Future
Cardiovascular & Hematological Agents in Medicinal Chemistry The Anti-Tumor Mechanism and Target of Triptolide Based on Network Pharmacology and Molecular Docking
Recent Patents on Anti-Cancer Drug Discovery Recent Advances in the Synthesis and Applications of Multimodal Gold-Iron Nanoparticles
Current Medicinal Chemistry Diabetes and Complications: Cellular Signaling Pathways, Current Understanding and Targeted Therapies
Current Drug Targets Domino/Cascade and Multicomponent Reactions for the Synthesis of Thiazole Derivatives
Current Organic Chemistry Expression and Functions of Heat Shock Proteins in the Normal and Pathological Mammalian Eye
Current Molecular Medicine Biological Activities of QIAPI 1 as a Melanin Precursor and Its Therapeutic Effects in Wistar Rats Exposed to Arsenic Poisoning
Central Nervous System Agents in Medicinal Chemistry Competition Between Tumor and Mononuclear Phagocyte System Causing the Low Tumor Distribution of Nanoparticles and Strategies to Improve Tumor Accumulation
Current Drug Delivery Drug Metabolism and Pharmacokinetics in Support of Drug Design
Current Pharmaceutical Design Current State of ERG as Biomarker in Prostatic Adenocarcinoma
Current Cancer Drug Targets Quinazolines as Apoptosis Inducers and Inhibitors: A Review of Patent Literature
Recent Patents on Anti-Cancer Drug Discovery Prognostic Value of MiRNAs in Patients with Laryngeal Cancer: A Systematic Review and Meta-Analysis
Current Cancer Drug Targets Emerging Features in the Regulation of MMP-9 Gene Expression for the Development of Novel Molecular Targets and Therapeutic Strategies
Current Drug Targets - Inflammation & Allergy