An integrated computational approach to screening of alkaloids inhibitors of TBX3 in breast cancer cell lines

Paul, Anjasu; Limon, Belayet Hasan; Hossain, Mobarok; Raza, Md. Thosif

doi:10.1080/07391102.2022.2046166

Cited by 5 publications

(3 citation statements)

References 73 publications

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“…The physiological condition of the simulation was 310 K and 1.013 bar, which mimics the physiological state of the human cell. 56 , 57 The energies and structures were recorded every 100 ps and saved in the trajectory, where 1000 frames were generated throughout the simulation. The Simulation Interaction Diagram module then examined the trajectories to investigate the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), 3D structure, and protein-ligand contact.…”

Section: Methodsmentioning

confidence: 99%

S-Adenosyl-l-Homocysteine Exhibits Potential Antiviral Activity Against Dengue Virus Serotype-3 (DENV-3) in Bangladesh: A Viroinformatics-Based Approach

Shill

Jahan

Alam

et al. 2023

Bioinform Biol Insights

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Dengue outbreak is one of the concerning issues in Bangladesh due to the annual outbreak with the alarming number of death and infection. However, there is no effective antiviral drug available to treat dengue-infected patients. This study evaluated and screened antiviral drug candidates against dengue virus serotype 3 (DENV-3) through viroinformatics-based analyses. Since 2017, DENV-3 has been the predominant serotype in Bangladesh. We selected 3 non-structural proteins of DENV-3, named NS3, NS4A, and NS5, as antiviral targets. Protein modeling and validation were performed with VERIFY-3D, Ramachandran plotting, MolProbity, and PROCHECK. We found 4 drug-like compounds from DRUGBANK that can interact with these non-structural proteins of DENV-3. Then, the ADMET profile of these compounds was determined by admetSAR2, and molecular docking was performed with AutoDock, SWISSDOCK, PatchDock, and FireDock. Furthermore, they were subjected to molecular dynamics (MD) simulation study using the DESMOND module of MAESTRO academic version 2021-4 (force field OPLS_2005) to determine their solution’s stability in a predefined body environment. Two drug-like compounds named Guanosine-5’-Triphosphate (DB04137) and S-adenosyl-l-homocysteine (DB01752) were found to have an effective binding with these 3 proteins (binding energy > 33.47 KJ/mole). We found NS5 protein was stable and equilibrated in a 100 ns simulation run along with a negligible (<3Å) root-mean-square fluctuation value. The root-mean-square deviation value of the S-adenosyl-l-homocysteine-NS5 complex was less than 3Å, indicating stable binding between them. The global binding energy of S-adenosyl-l-homocysteine with NS5 was −40.52 KJ/mole as ∆G. Moreover, these 2 compounds mentioned above are non-carcinogenic according to their ADMET (chemical absorption, distribution, metabolism, excretion, and toxicity) profile (in silico). These outcomes suggest the suitability of S-adenosyl-l-homocysteine as a potential drug candidate for dengue drug discovery research.

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Section: Methodsmentioning

confidence: 99%

S-Adenosyl-l-Homocysteine Exhibits Potential Antiviral Activity Against Dengue Virus Serotype-3 (DENV-3) in Bangladesh: A Viroinformatics-Based Approach

Shill

Jahan

Alam

et al. 2023

Bioinform Biol Insights

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show abstract

“…Concerning chemical reagents, an integrated computational approach indicated that two alkaloids, Jervine and Diflomotecan, can form stable complexes with TBX3 and suggested them as new effective drugs against breast cancers[ 63 ]. In another study, an aqueous extract of Fructus ligustri lucidi, a common Chinese herbal medicine, was reported to suppress TBX3 and enhance sensitivity to doxorubicin in colon cancer cells[ 64 ].…”

Section: Tbx3 As a Therapeutic Targetmentioning

confidence: 99%

Role of T-box transcription factor 3 in gastric cancers

Asano¹,

Imatani²,

Takeuchi³

et al. 2023

World J Gastrointest Pathophysiol

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The expression of T-box transcription factor 3 (TBX3) has been identified in various cancers, including gastric cancers. Its role in breast cancers and melanomas has been intensively studied, and its contribution to the progression of cancers through suppressing senescence and promoting epithelial-mesenchymal transition has been reported. Recent reports on the role of TBX3 in gastric cancers have implied its involvement in gastric carcinogenesis. Considering its pivotal role in the initiation and progression of cancers, TBX3 could be a promising therapeutic target for gastric cancers.

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“…Amir and colleagues reported that microRNA-206 suppressed TBX3 and, as a result, inhibited tumor growth of breast cancer organoids [ 62 ], which suggests the possibility that this microRNA could also regulate TBX3 in aging-related gastric cancers. With respect to the chemical inhibitor of TBX3, Paul and colleagues recently discovered that two alkaloids Jervine and Diflomotecan were able to form stable complexes with TBX3 through an integrated computational approach and that these two alkaloids could become new effective drugs for breast cancers [ 63 ]. Given their effect on TBX3, these two alkaloids may also be effective in treating aging-related gastric cancers.…”

Section: Future Perspectivesmentioning

confidence: 99%

Wnt Signaling and Aging of the Gastrointestinal Tract

Asano

Takeuchi

Imatani

et al. 2022

IJMS

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Aging is considered a risk factor for various diseases including cancers. In this aging society, there is an urgent need to clarify the molecular mechanisms involved in aging. Wnt signaling has been shown to play a crucial role in the maintenance and differentiation of tissue stem cells, and intensive studies have elucidated its pivotal role in the aging of neural and muscle stem cells. However, until recently, such studies on the gastrointestinal tract have been limited. In this review, we discuss recent advances in the study of the role of Wnt signaling in the aging of the gastrointestinal tract and aging-related carcinogenesis.

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An integrated computational approach to screening of alkaloids inhibitors of TBX3 in breast cancer cell lines

Cited by 5 publications

References 73 publications

S-Adenosyl-l-Homocysteine Exhibits Potential Antiviral Activity Against Dengue Virus Serotype-3 (DENV-3) in Bangladesh: A Viroinformatics-Based Approach

S-Adenosyl-l-Homocysteine Exhibits Potential Antiviral Activity Against Dengue Virus Serotype-3 (DENV-3) in Bangladesh: A Viroinformatics-Based Approach

Role of T-box transcription factor 3 in gastric cancers

Wnt Signaling and Aging of the Gastrointestinal Tract

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