Journal
ARCHIV DER PHARMAZIE
Volume 349, Issue 8, Pages 662-681Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/ardp.201600021
Keywords
Anticancer activity; Antifungal activity; Antimicrobial activity; Inhibitors; Triazoles
Funding
- Isfahan University of Medical Sciences, Isfahan, Iran [190068]
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The present study was planned to design some novel aldimine-type Schiff bases bearing 3,4,5-trimethoxyphenyl and 1,2,4-triazole-3-thione/thiol as potential tubulin polymerization inhibitors. The obtained results of the molecular docking study using the tubulin complex (PDB code: 1SA0) showed that compounds H-25 and H-26 were well fitted in the colchicine binding site of tubulin with binding energies of -8.68 and -8.40 kcal/mol, respectively, in comparison to the main ligand (-8.20 kcal/mol). In parallel, molecular simulations were also performed on five other 3,4,5-trimethoxyphenyl-containing ligand targets including hsp90, VEGFR2, and human and microbial (Staphylococcus aureus and Candida albicans) dihydrofolate reductase, among which H-17, H-45, H-27, H-02, and H-19 were the most suitable compounds, respectively. Evaluation of the cytotoxic effect of the most efficient compounds of the docking steps (H-25) revealed IC50 values of 12.48 +/- 1.10, 4.25 +/- 0.22, 3.33 +/- 0.31, and 9.71 +/- 0.75 mu M against the HT1080, HT29, MCF-7, and A549 cell lines, respectively, compared to doxorubicin (12.69 +/- 1.23, 6.12 +/- 0.47, 3.51 +/- 0.32, and 6.40 +/- 0.31 mu M, respectively). The in vitro tubulin polymerization investigation launched compounds H-25 and H-26 as potent antitubulin agents due to their IC50 values of 0.17 +/- 0.01 and 10.93 +/- 0.43 mu M, respectively.
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