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<p>Pyridine, 1,3,4-oxadiazole and 1,2,3-triazole are known for their wide range of biological properties such as anticancer, antifungal, antimicrobial and anti-tubercular activities. It is evident that Click reactions have evolved as one of the most powerful tools to deduce such types of heterocyclic moieties. In this study, a library of pyridine-linked 1,2,3-triazol-4-yl-1,3,4-oxadiazole derivatives was synthesized through a multi-step process. This involved the propargylation of 5-(2-arylaminopyridin-3-yl)-1,3,4-oxadiazole-2(3<i>H</i>)-thiones, followed by a Click reaction, to produce 2-(3-arylaminopyridin-3-yl)-5-[{(1-(aryl)-1<i>H</i>-1,2,3-triazol-4-yl)methyl}thio]-1,3,4-oxadiazoles. The synthesized compounds were characterized by elemental analysis, FT–IR, LC–MS, <sup>1</sup>H NMR, and <sup>13</sup>C NMR techniques. The electron donor properties of the derivatives were validated using a quantum chemical approach. The in vitro anticancer activity of the synthesized derivatives was evaluated against A549 (lung), HepG2 (liver), and PC-3 (prostate) cancer cell lines using the MTT assay, where compounds <b>4b, 4c, 4f, and 4k</b> demonstrated significant cytotoxicity. Clonogenic and wound healing assays revealed that compounds <b>4c</b> and <b>4f</b> effectively inhibited colony formation and cell migration in a time-dependent manner. In addition, compounds <b>4e</b> and <b>4c</b> exhibited notable antidiabetic potential by inhibiting α-amylase and α-glucosidase enzymes with IC<sub>50</sub> values of 46.53 ± 0.56, 49.31 ± 0.83&#xa0;µg/mL and 32.54 ± 0.89, 33.13 ± 1.02&#xa0;µg/mL, respectively, surpassing the activity of the standard drug acarbose. Molecular docking studies were conducted against the EGFR kinase domain (PDB ID: 1XKK), revealing favorable binding interactions for the active compounds, thereby supporting their potential mechanism of action at the molecular level. Collectively, these findings highlight the therapeutic promise of pyridine-linked oxadiazole-triazole hybrids as multifunctional agents with anticancer and antidiabetic activities.</p> Graphical abstract <p></p>

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Design and evaluation of pyridine-linked 1,3,4-oxadiazole-triazole heterocycles: a synthetic, computational and biological study

  • 期刊论文

  • 发表日期：

    2025年9月4日

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  • Boja Poojary,
  • Vishwa B. Das,
  • Vinuta Kamat,
  • Vinay C. Sangamesh,
  • Delicia Avilla Barreto,
  • Mahesh Akki,
  • Soukhyarani Gopal Nayak,
  • K. D. Venuprasad

摘要

Pyridine, 1,3,4-oxadiazole and 1,2,3-triazole are known for their wide range of biological properties such as anticancer, antifungal, antimicrobial and anti-tubercular activities. It is evident that Click reactions have evolved as one of the most powerful tools to deduce such types of heterocyclic moieties. In this study, a library of pyridine-linked 1,2,3-triazol-4-yl-1,3,4-oxadiazole derivatives was synthesized through a multi-step process. This involved the propargylation of 5-(2-arylaminopyridin-3-yl)-1,3,4-oxadiazole-2(3H)-thiones, followed by a Click reaction, to produce 2-(3-arylaminopyridin-3-yl)-5-[{(1-(aryl)-1H-1,2,3-triazol-4-yl)methyl}thio]-1,3,4-oxadiazoles. The synthesized compounds were characterized by elemental analysis, FT–IR, LC–MS, 1H NMR, and 13C NMR techniques. The electron donor properties of the derivatives were validated using a quantum chemical approach. The in vitro anticancer activity of the synthesized derivatives was evaluated against A549 (lung), HepG2 (liver), and PC-3 (prostate) cancer cell lines using the MTT assay, where compounds 4b, 4c, 4f, and 4k demonstrated significant cytotoxicity. Clonogenic and wound healing assays revealed that compounds 4c and 4f effectively inhibited colony formation and cell migration in a time-dependent manner. In addition, compounds 4e and 4c exhibited notable antidiabetic potential by inhibiting α-amylase and α-glucosidase enzymes with IC50 values of 46.53 ± 0.56, 49.31 ± 0.83 µg/mL and 32.54 ± 0.89, 33.13 ± 1.02 µg/mL, respectively, surpassing the activity of the standard drug acarbose. Molecular docking studies were conducted against the EGFR kinase domain (PDB ID: 1XKK), revealing favorable binding interactions for the active compounds, thereby supporting their potential mechanism of action at the molecular level. Collectively, these findings highlight the therapeutic promise of pyridine-linked oxadiazole-triazole hybrids as multifunctional agents with anticancer and antidiabetic activities.

Graphical abstract