Abstract
When a benzenesulfonyl moiety (BS) was bound to the N-piperazinyl ring of antibacterial fluoroquinolones (AMFQs) norfloxacin (NOR) or ciprofloxacin (CIP), the resulting benzenesulfonyl-fluoroquinolone (BSFQs) analogs showed an improved in vitro activity against Gram-positive strains. A bioisosterical replacement of the sulfonyl group for a carbonyl group led to the benzenecarboxamide-fluoroquinolones (BCFQs) that showed a similar trend in the antibacterial activity and spectrum. The BSFQs and BCFQs are considered members of the "dual targeting" fluoroquinolones, targeting both DNA gyrase and topoisomerase IV. To disclose the real contribution of the BS/BC moiety in anti-staphylococcal activity, a 3D-QSAR analysis that included calculation of theoretical molecular descriptors and pharmacophore generation was performed. Previous and present QSAR results have confirmed the positive influence on activity of small electron donating p-substituent on the BS or BC moiety. The generated phamacophore model showed that both phenyl and SO2/CO groups are involved in the interaction with receptor. We postulate that the enhanced potency of BSFQs against Staphylococcus aureus compared to CIP and NOR could be caused by the presence of the BS moiety that resulted in enhanced binding to DNA gyrase of Sa. Additionally, their greater ability to enter bacterial cells by diffusion and a reduced susceptibility to FQ-specific efflux pumps could also make a contribution.
Keywords: Benzenesulfonyl group, conformational analysis, fluoroquinolones, pharmacophore, QSAR, Staphylococcus, spectrum, benzenecarboxamide, bioisosterical, topoisomerase
Medicinal Chemistry
Title:SAR Analysis of New Dual Targeting Fluoroquinolones. Implications of the Benzenesulfonyl Group
Volume: 8 Issue: 3
Author(s): Marcelo J. Nieto, Adriana B. Pierini, Nidhi Singh, Christopher R. McCurdy, Ruben H. Manzo and aria R. Mazzieri
Affiliation:
Keywords: Benzenesulfonyl group, conformational analysis, fluoroquinolones, pharmacophore, QSAR, Staphylococcus, spectrum, benzenecarboxamide, bioisosterical, topoisomerase
Abstract: When a benzenesulfonyl moiety (BS) was bound to the N-piperazinyl ring of antibacterial fluoroquinolones (AMFQs) norfloxacin (NOR) or ciprofloxacin (CIP), the resulting benzenesulfonyl-fluoroquinolone (BSFQs) analogs showed an improved in vitro activity against Gram-positive strains. A bioisosterical replacement of the sulfonyl group for a carbonyl group led to the benzenecarboxamide-fluoroquinolones (BCFQs) that showed a similar trend in the antibacterial activity and spectrum. The BSFQs and BCFQs are considered members of the "dual targeting" fluoroquinolones, targeting both DNA gyrase and topoisomerase IV. To disclose the real contribution of the BS/BC moiety in anti-staphylococcal activity, a 3D-QSAR analysis that included calculation of theoretical molecular descriptors and pharmacophore generation was performed. Previous and present QSAR results have confirmed the positive influence on activity of small electron donating p-substituent on the BS or BC moiety. The generated phamacophore model showed that both phenyl and SO2/CO groups are involved in the interaction with receptor. We postulate that the enhanced potency of BSFQs against Staphylococcus aureus compared to CIP and NOR could be caused by the presence of the BS moiety that resulted in enhanced binding to DNA gyrase of Sa. Additionally, their greater ability to enter bacterial cells by diffusion and a reduced susceptibility to FQ-specific efflux pumps could also make a contribution.
Export Options
About this article
Cite this article as:
J. Nieto Marcelo, B. Pierini Adriana, Singh Nidhi, R. McCurdy Christopher, H. Manzo Ruben and R. Mazzieri aria, SAR Analysis of New Dual Targeting Fluoroquinolones. Implications of the Benzenesulfonyl Group, Medicinal Chemistry 2012; 8 (3) . https://dx.doi.org/10.2174/157340612800786633
DOI https://dx.doi.org/10.2174/157340612800786633 |
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
-
Cold Virus Fusion or Stopping Fusion Cold – Inhibitors of the Human Respiratory Syncytial Virus F Protein
Recent Patents on Anti-Infective Drug Discovery Sulfur-Containing Compounds in Protecting Against Oxidant-Mediated Lung Diseases
Current Medicinal Chemistry Locked Nucleic Acid Holds Promise in the Treatment of Cancer
Current Pharmaceutical Design Efficient Synthesis of Five and Six Member Sultam
Letters in Organic Chemistry Derivatives of Procaspase-Activating Compound 1 (PAC-1) and their Anticancer Activities
Current Medicinal Chemistry 3,4-DHQLO and Triazole and Its Related Analogues with Anticonvulsant Effects
Mini-Reviews in Medicinal Chemistry Review of the Published Literature Confirms the Safety of Intravenous Infusion of Mesenchymal Stem Cells
Current Stem Cell Research & Therapy Damage-Associated Molecular Patterns – Emerging Targets for Biologic Therapy of Childhood Arthritides
Inflammation & Allergy - Drug Targets (Discontinued) Prediction of Biological Activity Spectra for Substances: Evaluation on the Diverse Sets of Drug-Like Structures
Current Medicinal Chemistry Prevention, Diagnosis and Treatment of COVID-19: A Nanotechnological Perspective
Current Nanoscience Allopurinol Hypersensitivity Reactions: Desensitization Strategies and New Therapeutic Alternative Molecules
Inflammation & Allergy - Drug Targets (Discontinued) Synthesis and Biological Activities of New Halophenols
Medicinal Chemistry pH-Dependent Behavior of Novel Gellan Beads Loaded with Naproxen
Current Drug Delivery Meet Our Co-Editor
Current Psychopharmacology Epidermal Growth Factor Receptor and its Trafficking Regulation by Acetylation: Implication in Resistance and Exploring the Newer Therapeutic Avenues in Cancer
Current Topics in Medicinal Chemistry Multi-Kinase Inhibitors
Current Medicinal Chemistry Avian Flu; Pathogenesis and Therapy
Anti-Infective Agents A Novel Synthesis of Multisubstituted Pyrroles via Trisubstituted Olefins and TosMIC Derivatives
Letters in Organic Chemistry The Development of Ataxia Telangiectasia Mutated Kinase Inhibitors
Mini-Reviews in Medicinal Chemistry Targeting the Bombesin/Gastrin-Releasing Peptide Receptor to Treat Sepsis
Recent Patents on Anti-Infective Drug Discovery