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<p>Our previous studies found promising biological potentials of dipeptides containing sulphonamide functionality against various indications. In the present study, eight new dipeptide sulphonamides were synthesized. The initial reaction of L-proline and 4-methylbenzenesulphonyl chloride produced tosylproline in a good yield. The subsequent reaction of tosylproline with several substituted amino-N-phenylacetamides produced the dipeptides (<b>7a-h</b>) in good yields. Spectroscopic characterization of the compounds was done by Mass spectrometry, <sup>1</sup>H and <sup>13</sup>C NMR spectroscopies. In silico drug-likeness predictions revealed that all synthesized compounds complied with Lipinski’s and Veber’s rules, while ADMET studies confirmed their desirable drug-like properties. Molecular docking studies revealed strong binding of the synthesized compounds to the active sites of phosphodiesterase (PDE4) (4WCU), peroxisome proliferator-activated receptor alpha (PPARα) (5U46), and peroxidase (PRDX5) (1HD2) targets, corroborating the in vitro findings. Pharmacological studies revealed that compounds <b>7b</b>,<b> 7f</b>, and <b>7&#xa0;g</b> displayed high anti-diabetic and anti-inflammatory activity, in comparison to acarbose and indomethacin standards. Additionally, compound <b>7b</b> showed high anti-oxidant activity, with the IC<sub>50</sub> value of 0.721&#xa0;µg/mL, in comparison to ascorbic acid standard (IC<sub>50</sub> of 0.723&#xa0;µg/mL). Hence, these compounds can be considered as promising candidates for further evaluation.</p> Graphical Abstract <p></p>

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Dipeptide Tethered Sulphonamides as Anti-Diabetic, Anti-Inflammatory, and Anti-Oxidant Agent: Synthesis, Molecular Docking, and Drug-Likeness/ADMET Studies

  • 期刊论文

  • 发表日期：

    2025年4月16日

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  • Izuchi Solomon Attah,
  • Ifeoma Vivian Okonkwo,
  • Uchechukwu Chris Okoro,
  • Nkechi Orji,
  • Anayochukwu James Ezugwu,
  • Izuchukwu David Ugwu,
  • Collins Ibeji,
  • Onoabedje Efeturi Abraham,
  • Amaechi Lydia Ogara,
  • Surya Pratab Singh,
  • Ngozi Fidelia Ibeanu,
  • Chinweike Cosmas Eze

摘要

Our previous studies found promising biological potentials of dipeptides containing sulphonamide functionality against various indications. In the present study, eight new dipeptide sulphonamides were synthesized. The initial reaction of L-proline and 4-methylbenzenesulphonyl chloride produced tosylproline in a good yield. The subsequent reaction of tosylproline with several substituted amino-N-phenylacetamides produced the dipeptides (7a-h) in good yields. Spectroscopic characterization of the compounds was done by Mass spectrometry, 1H and 13C NMR spectroscopies. In silico drug-likeness predictions revealed that all synthesized compounds complied with Lipinski’s and Veber’s rules, while ADMET studies confirmed their desirable drug-like properties. Molecular docking studies revealed strong binding of the synthesized compounds to the active sites of phosphodiesterase (PDE4) (4WCU), peroxisome proliferator-activated receptor alpha (PPARα) (5U46), and peroxidase (PRDX5) (1HD2) targets, corroborating the in vitro findings. Pharmacological studies revealed that compounds 7b, 7f, and 7 g displayed high anti-diabetic and anti-inflammatory activity, in comparison to acarbose and indomethacin standards. Additionally, compound 7b showed high anti-oxidant activity, with the IC50 value of 0.721 µg/mL, in comparison to ascorbic acid standard (IC50 of 0.723 µg/mL). Hence, these compounds can be considered as promising candidates for further evaluation.

Graphical Abstract