Synthesis, in silico study, and anti-cancer activity of thiosemicarbazone derivatives

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Volume Title

A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Date

2021-10

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Mcode

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Language

en

Pages

19

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Biomedicines, Volume 9, issue 10

Abstract

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,1HNMR and13C 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 µg/mL to 14.25 µg/mL in 3-MBTSc and 2.80 µg/mL to 7.59 µg/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-β1, and BRAFV600E) indicated that both 4-NBTSc and 3-MBTSc potentially bind to TGF-β1 with the best binding energy of −42.34 Kcal/mol and −32.13 Kcal/mol, respectively. In addition, the test compound possesses desirable AD-MET 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.

Description

Funding Information: The authors would like to acknowledge Sharda University for their material support. Also, we would like to thank Richa Tandon in NIFTEM for her support during RT-qPCR work. Sonia Khanna and Piyush Kumar Gupta is also thankful to the School of Basic Sciences and Research, Sharda University, India for providing the infrastructure and facility for research. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

3-Methoxybenzaldehyde thiosemicarbazone, 4-Nitrobenzaldehyde thiosemicarbazone, B16-F0 melanoma, Cancer, In silico ADMET, MCF-7, Molecular docking

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Citation

Sibuh, B Z, Gupta, P K, Taneja, P, Khanna, S, Sarkar, P, Pachisia, S, Khan, A A, Jha, N K, Dua, K, Singh, S K, Pandey, S, Slama, P, Kesari, K K & Roychoudhury, S 2021, ' Synthesis, in silico study, and anti-cancer activity of thiosemicarbazone derivatives ', Biomedicines, vol. 9, no. 10, 1375 . https://doi.org/10.3390/biomedicines9101375