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Design, Synthesis, and Characterization of Novel Substituted Dihydrooxazoles: Biological Evaluation and Molecular Docking

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Abstract

A novel series of 2-[(2-R-4-fluoro-3-(methylsulfanyl)phenyl]-4,5-dihydro-1,3-oxazoles were designed, synthesized, and evaluated for their antibacterial and antioxidant activities against different microorganisms. The synthesized compounds were characterized by different spectral techniques like 1H and 13C NMR, IR, and mass spectroscopy. Derivatives with R = vinyl, isopropyl, H, and 4-chlorophenyl exhibited excellent antibacterial properties against S. aureus, P. aeruginosa, and E. coli. 4-Methylphenyl and 4-methoxy­phenyl analogs showed better activity against all the tested bacteria. Compounds with R = 4-methoxyphenyl and isopropyl displayed the highest DPPH radical scavenging activity with IC50 values of 24.39 and 25.29 µg/mL, respectively, and those with R = vinyl and isopropyl demonstrated excellent antioxidant activity according to the H2O2 radical scavenging assay with IC50 values of 20.24 and 18.76 µg/mL, respectively. Furthermore, molecular docking analysis revealed the highest binding energies, ΔG = –5.67, –5.33, and –5.13 kcal/mol for compounds with R = isopropyl, phenyl, and tert-butoxy, respectively, and hydrogen bonding interactions with the following amino acid residues of DNA gyrase subunit A of E. coli (PDB code: 4CKL): Arg15 (3.07 Å), Thr87 (2.28 Å), Gly16, Glu85, and Ile14.

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ACKNOWLEDGMENTS

A.T. Rao is thankful to CCST, IST, JNTUH University, Hyderabad, for providing laboratory and other facilities, CBT, IST, JNTUH for biological studies, and Osmania University for providing molecular modeling techniques.

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Authors and Affiliations

  1. Centre for Chemical Sciences and Technology, Institute of Science & Technology, Jawaharlal Nehru Technological University, 500085, Hyderabad, Telangana, India

    A. T. Rao, K. Naveen & A. J. Shree

  2. Department of Chemical Sciences, Indian Institute of Science Education and Research, 741246, Kolkata, West Bengal, India

    G. Mutyalanaidu

  3. Centre for Biotechnology, Department of Biotechnology, Institute of Science & Technology, Jawaharlal Nehru Technological University, 500085, Hyderabad, Telangana, India

    B. Venkanna

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  1. A. T. Rao
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  2. K. Naveen
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Rao, A.T., Naveen, K., Mutyalanaidu, G. et al. Design, Synthesis, and Characterization of Novel Substituted Dihydrooxazoles: Biological Evaluation and Molecular Docking. Russ J Org Chem 58, 125–135 (2022). https://doi.org/10.1134/S1070428022010183

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