Novel Aldimine Type Schiff Bases of 4 Amino 5 (3,4,5 trimethoxyphenyl)methyl] 1,2,4 triazole 3 thione/thiol: Docking Study, Synthesis, Biological Evaluation, and Anti Tubulin Activity
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 uM 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 uM, 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 uM, respectively.
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