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Design, one-pot synthesis, in silico ADMET prediction and molecular docking of novel triazolyl thiadiazine and thiazole derivatives with evaluation of antimicrobial, antioxidant and antibiofilm inhibition activity

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Abstract

A facile one pot multi-component synthesis of novel 1,3,4-thiadiazine and thiazole derivatives from the reaction of (methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethan-1-one, thiocarbohydrazide/or thiosemicarbazide, and aromatic aldehydes. The synthesized compounds were evaluated for antimicrobial, antibiofilm, and antioxidant activity. The results revealed the marked potency as antimicrobial agents. Thiazole 6e has the highest antimicrobial activity. Furthermore, most compounds inhibited biofilms produced by Pseudomonas aeruginosa. Promising thiazole 6c and thiadiazine derivatives (4c and 4 g) exhibited superior antioxidant activity and remarkable scavenging activity with DPPH, (86.99 ± 1.1, 81.54 ± 3.4 and 78.25 ± 1.8) and ABTS (80.06 ± 0.12, 62.29 ± 0.31 and 44.38 ± 0.20) respectively. The molecular docking simulation showed lower binding energy with different types of interaction at the active site of Dihydropteroate synthase, Sortase A, LasR, and Penicillin-binding proteins pockets indicating that these compounds could inhibit the enzyme and cause promising antimicrobial effects. Also, Molecular docking to the active sites of Peroxidase enzyme as an antioxidant receptor revealed that thiadiazine derivatives (4c and 4d) displayed minimal binding energy and have a good affinity toward the active pocket of each enzyme.

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Authors and Affiliations

  1. Chemical Industries Institute, National Research Centre, Dokki, Giza, 12622, Egypt

    Rizk E. Khidre, Eman Sabry & Ashraf A. Sediek

  2. Microbial Genetics Department, Biotechnology Research Institute, National Research Centre, Dokki, Giza, Egypt

    Ahmed F. El-Sayed

  3. Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo, Egypt

    Ahmed F. El-Sayed

Authors
  1. Rizk E. Khidre
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  2. Eman Sabry
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  3. Ahmed F. El-Sayed
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  4. Ashraf A. Sediek
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Contributions

REK: Conceptualization, Investigation, Supervision, Methodology, Writing – original draft. ES: Methodology, Investigation, Writing – review & editing. AFES: Methodology, Investigation, Writing – original draft. AAS: Methodology, Investigation, Writing – review & editing.

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Correspondence to Rizk E. Khidre or Ashraf A. Sediek.

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Khidre, R.E., Sabry, E., El-Sayed, A.F. et al. Design, one-pot synthesis, in silico ADMET prediction and molecular docking of novel triazolyl thiadiazine and thiazole derivatives with evaluation of antimicrobial, antioxidant and antibiofilm inhibition activity. J IRAN CHEM SOC 20, 2923–2947 (2023). https://doi.org/10.1007/s13738-023-02889-5

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