A New Class of Linezolid‐Based Molecules as Potential Antimicrobial and Antitubercular Agents: A Rational Approach. Issue 13 (1st April 2021)

• Record Type: Journal Article
• Authors: Kushwaha, Babita; Kushwaha, Narva Deshwar; Parish, Tanya; Guzman, Junitta; Kajee, Afsana; Shaikh, Mahamadhanif S.; Kehinde, Idowu; Obakachi, Vincent A.; Pathan, Tabasum Khan; Shinde, Suraj Raosaheb; Karpoormath, Rajshekhar
• Is Part Of: ChemistrySelect. Volume 6:Issue 13(2021)
• Page Start: 3065
• Page End: 3074
• Publication Date: 2021-04-01
• Subjects: ADME properties -- Antimicrobial activity -- Antitubercular activity -- Linezolid-like molecules -- Molecular docking.; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202100493
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: A total of 19 linezolid‐based novel molecules (6 a –d, 8 a –d and 10 a –k ) were synthesized by utilizing a simple and convenient synthetic method. Structures of all the novel derivatives were established by 1 H, 13 C NMR, FT‐IR and mass spectroscopic methods. In addition, structural elucidation of some representative compounds by 19 F, 2D NMR and single crystal X‐ray experiment's (6 d and 8 b ) further confirmed the structures of the desired compounds. All the final compounds were evaluated for their in vitro antitubercular ( Mycobacterium tuberculosis H37 RV strain), antibacterial ( S. aureus, B. subtilis, E. coli and P. aeruginosa ) and antifungal ( C. neoformans, C. albicans and A. niger ) activities. The docking study of most active compounds were also performed towards 50S ribosomal unit of Haloarcula marismortui . The Lipinski's rule of five and significant ADME pharmacokinetic parameters were also analysed indicating potential to develop good oral antimicrobial and antitubercular drug candidates. Abstract : Linezolid‐based novel molecules were synthesized by utilizing a simple and convenient synthetic method. All the novel derivatives were established by 1 H, 13 C NMR, FT‐IR and mass spectroscopic methods and evaluated for their in vitro antitubercular and antimicrobial activity. The best active compounds and linezolid were docked against bacterial ribosomes to determine their potential to inhibit the formation of a functional 70S initiation complex. The Lipinski′s rule of five and significant ADME pharmacokinetic parameters were also analysed.