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2000
Volume 22, Issue 2
  • ISSN: 1573-4072
  • E-ISSN: 1875-6646

Abstract

Objective

Hybridizing 1,3,4-oxadiazole with other anticancer heterocyclic pharmacophores improves the capacity of novel drug candidates to overcome drug resistance. In this study, we designed and synthesized a new series of oxadiazole derivatives based on these biological implications as part of our continuous interest in designing and developing novel therapeutic medicines.

Methods

The final derivatives of substituted N-1,3,4-oxadiazol-2-amine were achieved through the conventional synthesis method, and the physicochemical and spectroscopic results validated the newly synthesized compounds' structural integrity. The docking studies revealed that compound AL45 (-11.1 k/cal) showed similar binding affinity of standard molecule clorgyline towards the targeted protein, and these molecules showed 2 conventional hydrogen bonds with Tyr 407 and Met 445 amino acid residues. The entire 10 synthesized compounds were evaluated for their cytotoxicity by MTT assay using MCF-7 and A549 cell lines.

Results

The A549 cell line showed the most promising sensitivity towards all the synthesized molecules, but the compounds AL41 (32.35 ± 0.11 nM), AL45 (24.37 ± 0.253 nM), and AL49 (37.45 ± 0.041 nM) were most promising derivatives. The MCF-7 cell line showed sensitivity towards the following derivatives, such as AL41 (29.32 ± 0.861 nM), AL45 (24.85± 0.846 nM), AL49 (33.93 ± 0.333 nM), and AL43 (27.27 ± 0.423 nM).

Conclusion

These compounds showed promise in inhibiting the proliferation of tumor cells. These chemicals also demonstrated a higher docking score and inhibition of the human MAO-A enzyme. In addition, the ADMET screening revealed that all the designed compounds have low toxicity and adequate pharmacokinetic properties.

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Synthesis and In-vitro Cytotoxicity Activity of 1,3,4-oxadiazol-2-amine Derivatives and Inhibition of Human MAO-A Enzyme: A Molecular Docking Approach
Curr. Bioact. Compd. 22, E15734072341329 (2026); https://doi.org/10.2174/0115734072341329240926101645
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  • Article Type:     Research Article
Keyword(s): ADMET screening; docking studies; human MAO-A enzyme; hydrogen bond; MTT assay; Oxadiazole

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