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

Sibuh, BZ; Gupta, PK; Taneja, P; Khanna, S; Sarkar, P; Pachisia, S; Khan, AA; Jha, NK; Dua, K; Singh, SK; Pandey, S; Slama, P; Kesari, KK; Roychoudhury, S

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

Sibuh, BZ Gupta, PK Taneja, P Khanna, S Sarkar, P Pachisia, S Khan, AA Jha, NK Dua, K

Singh, SK Pandey, S Slama, P Kesari, KK Roychoudhury, S

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Publisher:: MDPI AG
Publication Type:: Journal Article
Citation:: Biomedicines, 9, (10), pp. 1375-1375

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Field	Value	Language
dc.contributor.author	Sibuh, BZ
dc.contributor.author	Gupta, PK
dc.contributor.author	Taneja, P
dc.contributor.author	Khanna, S
dc.contributor.author	Sarkar, P
dc.contributor.author	Pachisia, S
dc.contributor.author	Khan, AA
dc.contributor.author	Jha, NK
dc.contributor.author	Dua, K https://orcid.org/0000-0002-7507-1159
dc.contributor.author	Singh, SK
dc.contributor.author	Pandey, S
dc.contributor.author	Slama, P
dc.contributor.author	Kesari, KK
dc.contributor.author	Roychoudhury, S
dc.date.accessioned	2021-10-06T11:40:15Z
dc.date.available	2021-10-06T11:40:15Z
dc.identifier.citation	Biomedicines, 9, (10), pp. 1375-1375
dc.identifier.issn	2227-9059
dc.identifier.uri	http://hdl.handle.net/10453/150868
dc.description.abstract	<jats:p>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 and 13C 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 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.</jats:p>
dc.language	en
dc.publisher	MDPI AG
dc.relation.ispartof	Biomedicines
dc.relation.isbasedon	10.3390/biomedicines9101375
dc.rights	info:eu-repo/semantics/openAccess
dc.title	Synthesis, in Silico Study, and Anti-Cancer Activity of Thiosemicarbazone Derivatives
dc.type	Journal Article
utslib.citation.volume	9
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Graduate School of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Graduate School of Health/GSH.Pharmacy
utslib.copyright.status	open_access	*
dc.date.updated	2021-10-06T11:40:14Z
pubs.issue	10
pubs.publication-status	Published online
pubs.volume	9
utslib.citation.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 and 13C 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 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.

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