Abstract
Mycobacteria represent a group of pathogens which cause serious diseases in mammals, including the lethal tuberculosis (Mycobacterium tuberculosis). Despite the mortality of this community-acquired and nosocomial disease mentioned above, other mycobacteria may cause similar infections, acting as dangerous opportunistic pathogens. Additionally, resistant strains belonging to Mycobacterium spp. have emerged. Thus, the design of novel antimycobacterial agents is a challenge for the scientific community. In this sense, chemoinformatics has played a vital role in drug discovery, helping to rationalize chemical synthesis, as well as the evaluation of pharmacological and ADMET (absorption, distribution, metabolism, excretion, toxicity) profiles in both medicinal and pharmaceutical chemistry. Until now, there is no in silico methodology able to assess antimycobacterial activity and ADMET properties at the same time. This work introduces the first multitasking model based on quantitative-structure biological effect relationships (mtk-QSBER) for simultaneous prediction of antimycobacterial activities and ADMET profiles of drugs/chemicals under diverse experimental conditions. The mtk-QSBER model was constructed by using a large and heterogeneous dataset of compounds (more than 34600 cases), displaying accuracies higher than 90% in both, training and prediction sets. To illustrate the utility of the present model, several molecular fragments were selected and their contributions to different biological effects were calculated and analyzed. Also, many properties of the investigational drug TMC-207 were predicted. Results confirmed that, from one side, TMC-207 can be a promising antimycobacterial drug, and on the other hand, this study demonstrates that the present mtk-QSBER model can be used for virtual screening of safer antimycobacterial agents.
Keywords: ADMET, antimycobacterial, fragment, linear discriminant analysis, mtk-QSBER, spectral moments.
Current Topics in Medicinal Chemistry
Title:Simultaneous Modeling of Antimycobacterial Activities and ADMET Profiles: A Chemoinformatic Approach to Medicinal Chemistry
Volume: 13 Issue: 14
Author(s): Alejandro Speck-Planche and M. N.D.S. Cordeiro
Affiliation:
Keywords: ADMET, antimycobacterial, fragment, linear discriminant analysis, mtk-QSBER, spectral moments.
Abstract: Mycobacteria represent a group of pathogens which cause serious diseases in mammals, including the lethal tuberculosis (Mycobacterium tuberculosis). Despite the mortality of this community-acquired and nosocomial disease mentioned above, other mycobacteria may cause similar infections, acting as dangerous opportunistic pathogens. Additionally, resistant strains belonging to Mycobacterium spp. have emerged. Thus, the design of novel antimycobacterial agents is a challenge for the scientific community. In this sense, chemoinformatics has played a vital role in drug discovery, helping to rationalize chemical synthesis, as well as the evaluation of pharmacological and ADMET (absorption, distribution, metabolism, excretion, toxicity) profiles in both medicinal and pharmaceutical chemistry. Until now, there is no in silico methodology able to assess antimycobacterial activity and ADMET properties at the same time. This work introduces the first multitasking model based on quantitative-structure biological effect relationships (mtk-QSBER) for simultaneous prediction of antimycobacterial activities and ADMET profiles of drugs/chemicals under diverse experimental conditions. The mtk-QSBER model was constructed by using a large and heterogeneous dataset of compounds (more than 34600 cases), displaying accuracies higher than 90% in both, training and prediction sets. To illustrate the utility of the present model, several molecular fragments were selected and their contributions to different biological effects were calculated and analyzed. Also, many properties of the investigational drug TMC-207 were predicted. Results confirmed that, from one side, TMC-207 can be a promising antimycobacterial drug, and on the other hand, this study demonstrates that the present mtk-QSBER model can be used for virtual screening of safer antimycobacterial agents.
Export Options
About this article
Cite this article as:
Speck-Planche Alejandro and Cordeiro N.D.S. M., Simultaneous Modeling of Antimycobacterial Activities and ADMET Profiles: A Chemoinformatic Approach to Medicinal Chemistry, Current Topics in Medicinal Chemistry 2013; 13 (14) . https://dx.doi.org/10.2174/15680266113139990116
DOI https://dx.doi.org/10.2174/15680266113139990116 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
- Announcements
Related Articles
-
Plant Natural Products as a Potential Source for Antibacterial Agents: Recent Trends
Anti-Infective Agents in Medicinal Chemistry Targeting the Peptide Deformylase of Mycobacterium tuberculosis Leads to Drug Discovery
Letters in Drug Design & Discovery Tuberculous Lymphadenitis in Southern Italy: Clinical Aspects and Treatment Perspectives
Anti-Infective Agents Recent Patents of Gene Sequences Relative to DNA Polymerases
Recent Patents on DNA & Gene Sequences Host-Cell Survival and Death During Chlamydia Infection
Current Immunology Reviews (Discontinued) SAR, QSAR and Docking of Anticancer Flavonoids and Variants: A Review
Current Topics in Medicinal Chemistry Synthesis of Pyrophosphate-Containing Compounds that Stimulate VγVδ2 T Cells: Application to Cancer Immunotherapy
Medicinal Chemistry Relevance of Pharmacokinetic and Pharmacodynamic Modeling to Clinical Care of Critically Ill Patients
Current Pharmaceutical Biotechnology New Synthetic Antibiotics for the Treatment of Enterococcus and Campylobacter Infection
Current Topics in Medicinal Chemistry In Vitro Anti-mycobacterial Activity of Three Medicinal Plants of Lamiaceae Family
Recent Patents on Anti-Infective Drug Discovery Bacterial Infection Probes and Imaging Strategies in Clinical Nuclear Medicine and Preclinical Molecular Imaging
Current Topics in Medicinal Chemistry Why is the Incidence of Type 1 Diabetes Increasing?
Current Diabetes Reviews Design and Development of ChemInfoCloud: An Integrated Cloud Enabled Platform for Virtual Screening
Combinatorial Chemistry & High Throughput Screening Identification and Characterization of a Novel Oligomeric Decaprenyl Diphosphate Synthase
Protein & Peptide Letters Management of Certain Respiratory Disorders through Ayurveda: A Systematic Review of Clinical Studies Published in Ayurveda Journal
Current Traditional Medicine Association of Low Vitamin D with Complications of HIV and AIDS: A literature Review
Infectious Disorders - Drug Targets Recent Developments in the Electrochemistry of Some Nitro Compounds of Biological Significance
Current Organic Chemistry Tuberculosis, BCG Vaccination, and COVID-19: Are They Connected?
Mini-Reviews in Medicinal Chemistry Recent Patents Regarding Essential Oils and the Significance of their Constituents in Human Health and Treatment
Recent Patents on Anti-Infective Drug Discovery Transcriptional Regulation of Antimicrobial Host Defense Peptides
Current Protein & Peptide Science