Molecular docking, synthesis and anticancer activity of thiosemicarbazone derivatives against MCF-7 human breast cancer cell line

Sibuh, Belay Zeleke; Khanna, Sonia; Taneja, Pankaj; Sarkar, Paratpar; Taneja, Neetu Kumra

doi:10.1016/j.lfs.2021.119305

Cited by 27 publications

(13 citation statements)

References 65 publications

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“…Total mRNA was isolated and extracted by Trizol reagent as described in an earlier method [62,63]. RevertAid First Strand cDNA synthesis kit (Thermo Fisher Scientific, Waltham, Massachusetts, USA) was used to synthesize cDNA in a total reaction volume of 20 µL containing oligo-dT primers, RiboLock RNase inhibitor, and reverse transcriptase.…”

Section: Gene Expression Analysismentioning

confidence: 99%

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

et al. 2021

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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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Section: Gene Expression Analysismentioning

confidence: 99%

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

et al. 2021

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Section: Introductionmentioning

confidence: 99%

“…This biological activity is frequently associated with their ability to block the enzyme ribonucleotide reductase, as shown with powerful anticancer medications such as triapine. [33,34] Furthermore, because of its biological activity, the thiophene nucleus has received increased attention. It has been discovered in a number of potential anticancer medicines, including raltitrexed (Tomudex ® ), which induces DNA fragmentation and consequent cell death by inhibiting the thymidylate synthase enzyme.…”

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confidence: 99%

Synthesis, density functional theory calculation, molecular docking studies, and evaluation of novel 5‐nitrothiophene derivatives for anticancer activity

Nuha

Evren

Çiyanci

et al. 2022

Archiv der Pharmazie

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Within the scope of this study, new 2-{2-[(5-nitrothiophen-2-yl)methylene] hydrazinyl}thiazole derivatives (2a-j) were synthesized and investigated for their potential anticancer and enzyme inhibition activities. Spectroscopic techniques were used to determine the structures of substances. The anticancer activities of compounds were detected in A549 human lung carcinoma and L929 murine fibroblast cell lines, determining cytotoxicity, apoptosis, mitochondrial membrane integrity, and caspase-3 activation. Compounds 2b bearing 4-nitrophenyl, 2c bearing phenyl, and 2d bearing 4-cyanophenyl moieties were specified with high anticancer activity, acting through an apoptotic pathway with an apoptosis ratio of 9.61%-15.59%. Mitochondrial membrane depolarization was determined to be 25.53% and 22.33% for compounds 2b and 2c, respectively. Furthermore, compound 2c exhibited excellent caspase-3 activation. A molecular docking study was realized with compound 2c on the caspase-3 enzyme. Furthermore, the electronic characteristics of the active compounds were investigated using density functional theory (DFT) at the B3LYP/6-31G (d, p) level. The frontier molecular orbital energy and atomic net charges were examined.

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“…Cancer is the leading cause of death worldwide, with a projected 19.3 million new cases reported and approximately 10 million deaths in 2020. It has been estimated that about 26 million new cases and 17 million deaths by 2030 [ 1 , 2 ]. Cancer develops when normal cells are transformed into cancer cells that usually evolve in a multi-stage and multi-step process from the pre-cancerous lesions to malignant (cancerous) tumors.…”

Section: Introductionmentioning

confidence: 99%

Phytoconstituents of Withania somnifera unveiled Ashwagandhanolide as a potential drug targeting breast cancer: Investigations through computational, molecular docking and conceptual DFT studies

Gowtham¹,

Murali

Singh

et al. 2022

PLoS ONE

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Breast cancer is the second most common malignancy in females worldwide and poses a great challenge that necessitates the identification of novel therapeutic agents from several sources. This research aimed to study the molecular docking and molecular dynamics simulations of four proteins (such as PDB: 6CBZ, 1FDW, 5GWK and 2WTT) with the selected phytochemicals from Withania somnifera to identify the potential inhibitors for breast cancer. The molecular docking result showed that among 44 compounds, two of them, Ashwagandhanolide and Withanolide sulfoxide have the potential to inhibit estrogen receptor alpha (ERα), 17-beta-hydroxysteroid -dehydrogenase type 1 (17β-HSD1), topoisomerase II alpha (TOP2A) and p73 tetramerization domain that are expressed during breast cancer. The molecular dynamics (MD) simulations results suggested that Ashwagandhanolide remained inside the binding cavity of four targeted proteins and contributed favorably towards forming a stable protein-ligand complex throughout the simulation. Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties confirmed that Ashwagandhanolide is hydrophobic and has moderate intestinal permeability, good intestinal absorption, and poor skin permeability. The compound has a relatively low VDss value (-1.652) and can be transported across ABC transporter and good central nervous system (CNS) permeability but did not easily cross the blood-brain barrier (BBB). This compound does not possess any mutagenicity, hepatotoxicity and skin sensitization. Based on the results obtained, the present study highlights the anticancer potential of Ashwagandhanolide, a compound from W. somnifera. Furthermore, in vitro and in vivo studies are necessary to perform before clinical trials to prove the potentiality of Ashwagandhanolide.

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Molecular docking, synthesis and anticancer activity of thiosemicarbazone derivatives against MCF-7 human breast cancer cell line

Cited by 27 publications

References 65 publications

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

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

Synthesis, density functional theory calculation, molecular docking studies, and evaluation of novel 5‐nitrothiophene derivatives for anticancer activity

Phytoconstituents of Withania somnifera unveiled Ashwagandhanolide as a potential drug targeting breast cancer: Investigations through computational, molecular docking and conceptual DFT studies

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