2. Academic Validation
  3. Novel linezolid-based oxazolidinones as potent anticandidiasis and antitubercular agents

Novel linezolid-based oxazolidinones as potent anticandidiasis and antitubercular agents

  • Bioorg Chem. 2022 Sep;126:105869. doi: 10.1016/j.bioorg.2022.105869.
Shaik Faazil 1,  M Shaheer Malik 2,  Saleh A Ahmed 3,  Reem I Alsantali 4,  Poornachandra Yedla 5,  Meshari A Alsharif 6,  Iqbal N Shaikh 7,  Ahmed Kamal 8
Affiliations

Affiliations

  • 1 Department of Chemistry, Poona College of Arts, Science and Commerce, Pune 411001, India; Department of Medicinal Chemistry and Pharmacology, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India.
  • 2 Department of Chemistry, Faculty of Applied Sciences, Umm Al-Qura University, Makkah 21955, Saudi Arabia. Electronic address: msmalik@uqu.edu.sa.
  • 3 Department of Chemistry, Faculty of Applied Sciences, Umm Al-Qura University, Makkah 21955, Saudi Arabia; Department of Chemistry, Faculty of Science, Assiut University, Assiut 71516, Egypt. Electronic address: saahmed@uqu.edu.sa.
  • 4 Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Taif 21944, Saudi Arabia.
  • 5 Division of Applied Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 085, India.
  • 6 Department of Chemistry, Faculty of Applied Sciences, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
  • 7 Department of Chemistry, Poona College of Arts, Science and Commerce, Pune 411001, India.
  • 8 Department of Medicinal Chemistry and Pharmacology, CSIR - Indian Institute of Chemical Technology, Hyderabad 500007, India; Department of Pharmacy, Birla Institute of Technology & Science, Pilani, Hyderabad 500078, India. Electronic address: ahmedkamal@iict.res.in.
PMID: 35598571 DOI: 10.1016/j.bioorg.2022.105869
Abstract

The quest for new Antifungal and antitubercular drugs is a need of the hour because of morbid co-pathogenesis and an increase in immunocompromised patients. One of the ways forward is to explore and repurpose the established pharmacophores for the desired application. Oxazolidinones are well-known Antibacterial agents, with few investigations reported to exploit their Antifungal properties. Herein, we report the design and synthesis of a series of linezolid-based oxazolidinones as potent anticandidiasis and antitubercular agents. Studies revealed that two of the novel oxazolidinones 2 and 3a exhibited excellent anticandidiasis activity against different Candida fungus strains, superior to standard drugs. Mechanistic and docking studies revealed that oxazolidinones were better inhibitors of the ergosterol biosynthesis pathway than the controls used. In addition, the oxazolidinones 2 and 3a also exhibited prominent inhibitory activity against M. tuberculosis H37Rv with MIC values of 1 and 2 μg/ml, respectively. Computational studies demonstrated the binding of the compounds to the transcriptional regulatory repressor protein, which was reinforced by the molecular dynamics simulations. The pharmacophore modeling experiments validated the molecular docking results in both the target proteins.

Keywords

Anticandidiasis; Antifungal; Antitubercular; Molecular dynamics; Oxazolidinone; Pharmacophore modeling.

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