Synthesis, In Silico Study, and Anti-Cancer Activity of Thiosemicarbazone Derivatives

Thiosemicarbazones are known for their biological and pharmacological activities. In this study, we have synthesized and characterized 3-Methoxybenzaldehyde thiosemicarbazone (3-MBTSc) and 4-Nitrobenzaldehyde thiosemicarbazone (4-NBTSc) using IR, (HNMR)-H-1 and C-13 NMR. The compound's in vitro anticancer activities against different cell lines were evaluated. Molecular docking, Insilco ADMET, and drug-likeness prediction were also done. The test compounds showed a comparative IC50 and growth inhibition with the standard drug Doxorubicin. The IC50 ranges from 2.82 mu g/mL to 14.25 mu g/mL in 3-MBTSc and 2.80 mu g/mL to 7.59 mu g/mL in 4-NBTSc treated cells. The MTT assay result revealed, 3-MBTSc inhibits 50.42 and 50.31 percent of cell growth in B16-F0 and EAC cell lines, respectively. The gene expression showed that tumor suppressor genes such as PTEN and BRCA1 are significantly upregulated in 7.42 and 5.33 folds, and oncogenes, PKC, and RAS are downregulated -7.96 and -7.64 folds, respectively in treated cells. The molecular docking performed on the four targeted proteins (PARP, VEGFR-1, TGF-beta 1, and BRAF(V600E)) indicated that both 4-NBTSc and 3-MBTSc potentially bind to TGF-beta 1 with the best binding energy of -42.34 Kcal/mol and -32.13 Kcal/mol, respectively. In addition, the test compound possesses desirable ADMET and drug-likeness properties. Overall, both 3-MBTSc and 4-NBTSc have the potential to be multitargeting drug candidates for further study. Moreover, 3-MBTSc showed better activity than 4-NBTSc.

Automated summary

Thiosemicarbazones, namely 3-MBTSc and 4-NBTSc, were synthesized and characterized, showing comparable anticancer activities with Doxorubicin. In vitro assays revealed growth inhibition in treated cells, along with gene expression changes in tumor suppressor and oncogenes. Molecular docking indicated potential binding to TGF-beta 1, with favorable ADMET and drug-likeness properties, suggesting both compounds as multitargeting drug candidates for further study, with 3-MBTSc exhibiting better activity.