Background: Benzotriazole-based compounds with various outstanding bioactivities have become increasingly
active in the field of medicinal chemistry. Importantly, some anticancer benzotriazole compounds such as vorozole and TBB
have been clinically used. It can be reasonable to expect that benzotriazole derivatives will play remarkable roles in medicinal
field.
Methods: The in silico molecular docking and ADMET studies of the designed compounds were performed on binding
cavity of Legumain using Schrodinger 2021-3. New mannich base derivatives of benzotriazoles (6a-p) were synthesized and
these compounds were characterized by 1HNMR, 13CNMR and mass spectral data. These compounds (6a-p) were
investigated for their anticancer propertiestowards four different human cancer cell lines by utilize of MTT method.
Results: The IFD results are in agreement with those of XP docking studies, confirming the binding of the test compounds
in the binding site of legumain. The predicted ADMET properties of compounds fall within the acceptable range. Most of
the compounds were displayed good to moderate anticancer activities to compare with control drug. The compounds
showed IC50 valuesrange from 0.012±0.001 to 22.9±9.11 µM, and positive control showed values from 0.13 ± 0.017to 3.08
± 0.135µM. Among synthesized compounds, these 6a, 6c, 6e, 6f, 6j, 6n and 6p were demonstrated more potent anticancer
activities than etoposide.
Conclusion: Among all the synthesized compounds the compound 6a contain electron-donating(3,5-dimethoxy) group on
the phenyl ring displayed highest anticancer activity on four cancer cell lines with IC50 values as MCF-7=0.012±0.001µM,
A549=0.18±0.076µM, Colo- 205=0.34±0.083µM and A2780= 0.07±0.006µM, respectively.
Key words: MCF-7, A549, Colo-205, A2780, Benzotriazole, In silico, ADMET and MTT Assay
|
