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
Vijayalakshmi M. K, Srinivasan RObjective:
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 in-vitro 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 A41 (32.35 ± 0.11nM), AL45 (24.37 ± 0.253nM), and AL49 (37.45 ± 0.041nM) were most promising derivatives. The MCF-7 cell line showed sensitivity towards the following derivatives, such as AL41 (29.32 ± 0.861nM), AL45 (27.27 ± 0.423nM), AL49 (33.93 ± 0.333nM), and AA8 (39.328 ± 0.11nM).
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 in-silico ADMET screening revealed that all the designed compounds have low toxicity and adequate pharmacokinetic properties.