Structure-activity relationship of dicoumarol derivatives as anti- staphylococcus aureus (Staph infection) agents

Nidaa Rasheed, Natalie J. Galant, I. Csizmadia

Research output: Contribution to journalArticle

Abstract

Introduction: Staph infection, caused by a bacterium known as Staphylococcus aureus, results in a range of diseases from cellulitis to meningitis. Dicoumarol compounds are now emerging as new anti-Staph infection agents as they possess a different chemical structure than compounds used in previous treatments, in order to combat antibiotic-resistant strains. However, it is unclear how such chemical modulations to the dicoumarol backbone structure achieve higher drug performance.  Methods: The following review analyzed various quantitative structure-activity relationship (QSAR) studies on dicoumarol compounds and compared them against the corresponding minimum inhibitory concentration and binding affinity values.  Results: Compared to the antimicrobial activity, the dicoumarol derivatives with electron withdrawing substituents, CL, NO2 and CF3 showed an inverse correlation; whereas, the opposite was observed with electron donating compounds such as OH, OMe, and amine groups. Based on the interactions of dicoumarol at the active site, an “aromatic donor-acceptor” relationship was proposed as the method of action for this drug. Furthermore, substituent positioning on the benzene ring was found to exert a greater effect on the binding affinity, speculating that the mechanism of action is two characteristics based, needing, both, the proper aromatic pi-pi interaction for stabilization and direct binding to the OH group in the Tyrosine residue, affected by the steric hindrance.  Conclusion: This foundational review can enhance productivity sought by the pharmaceutical agency to use combinational chemistry to increase the efficiency to discover new hits in the synthesis of dicoumarol drugs against Staph infection.

Original languageEnglish
Pages (from-to)93-98
Number of pages6
JournalAnti-Infective Agents
Volume17
Issue number2
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Dicumarol
Structure-Activity Relationship
Staphylococcus aureus
Infection
Pharmaceutical Preparations
Electrons
Cellulitis
Quantitative Structure-Activity Relationship
Microbial Sensitivity Tests
Benzene
Meningitis
Amines
Tyrosine
Catalytic Domain
Anti-Bacterial Agents
Bacteria

Keywords

  • Computational chemistry
  • Dicoumarol derivatives
  • Pi-stacking
  • S. aureus
  • Staph infection
  • Thermodynamics

ASJC Scopus subject areas

  • Pharmacology
  • Infectious Diseases

Cite this

Structure-activity relationship of dicoumarol derivatives as anti- staphylococcus aureus (Staph infection) agents. / Rasheed, Nidaa; Galant, Natalie J.; Csizmadia, I.

In: Anti-Infective Agents, Vol. 17, No. 2, 01.01.2019, p. 93-98.

Research output: Contribution to journalArticle

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